2024/04/19 更新

写真a

ヨシダ マサシ
吉田 賢司
YOSHIDA Masashi
所属
医歯薬学域 講師
職名
講師
外部リンク

学位

  • 博士(医学) ( 2008年3月   岡山大学 )

 

論文

  • In vivo tracking transplanted cardiomyocytes derived from human induced pluripotent stem cells using nuclear medicine imaging

    Yukihiro Saito, Naoko Nose, Toshihiro Iida, Kaoru Akazawa, Takayuki Kanno, Yuki Fujimoto, Takanori Sasaki, Masaru Akehi, Takahiro Higuchi, Satoshi Akagi, Masashi Yoshida, Toru Miyoshi, Hiroshi Ito, Kazufumi Nakamura

    Frontiers in Cardiovascular Medicine   10   2023年9月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Frontiers Media SA  

    Introduction

    Transplantation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is a promising treatment for heart failure. Information on long-term cell engraftment after transplantation is clinically important. However, clinically applicable evaluation methods have not yet been established.

    Methods

    In this study, to noninvasively assess transplanted cell engraftment, human SLC5A5, which encodes a sodium/iodide symporter (NIS) that transports radioactive tracers such as 125I, 18F-tetrafluoroborate (TFB), and 99mTc-pertechnetate (99mTcO4), was transduced into human induced pluripotent stem cells (iPSCs), and nuclear medicine imaging was used to track engrafted human iPSC-CMs.

    Results

    To evaluate the pluripotency of NIS-expressing human iPSCs, they were subcutaneously transplanted into immunodeficient rats. Teratomas were detected by 99mTcO4 single photon emission computed tomography (SPECT/CT) imaging. NIS expression and the uptake ability of 125I were maintained in purified human iPSC-CMs. NIS-expressing human iPSC-CMs transplanted into immunodeficient rats could be detected over time using 99mTcO4 SPECT/CT imaging. Unexpectedly, NIS expression affected cell proliferation of human iPSCs and iPSC-derived cells.

    Discussion

    Such functionally designed iPSC-CMs have potential clinical applications as a noninvasive method of grafted cell evaluation, but further studies are needed to determine the effects of NIS transduction on cellular characteristics and functions.

    DOI: 10.3389/fcvm.2023.1261330

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  • Evidence for Hypoxia-Induced Shift in ATP Production from Glycolysis to Mitochondrial Respiration in Pulmonary Artery Smooth Muscle Cells in Pulmonary Arterial Hypertension

    Satoshi Akagi, Kazufumi Nakamura, Megumi Kondo, Satoshi Hirohata, Heiichiro Udono, Mikako Nishida, Yukihiro Saito, Masashi Yoshida, Toru Miyoshi, Hiroshi Ito

    Journal of Clinical Medicine   12 ( 15 )   5028 - 5028   2023年7月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    Background: The metabolic state of pulmonary artery smooth muscle cells (PASMCs) from patients with pulmonary arterial hypertension (PAH) is not well understood. In this study, we examined the balance between glycolysis and mitochondrial respiration in non-PAH-PASMCs and PAH-PASMCs under normoxia and hypoxia. Methods: We investigated the enzymes involved in glycolysis and mitochondrial respiration, and studied the two major energy-yielding pathways (glycolysis and mitochondrial respiration) by measuring extracellular acidification rate (ECAR) and cellular oxygen consumption rate (OCR) using the Seahorse extracellular flux technology. Results: Under both normoxia and hypoxia, the mRNA and protein levels of pyruvate dehydrogenase kinase 1 and pyruvate dehydrogenase were increased in PAH-PASMCs compared with non-PAH-PASMCs. The mRNA and protein levels of lactate dehydrogenase, as well as the intracellular lactate concentration, were also increased in PAH-PASMCs compared with non-PAH-PASMCs under normoxia. However, these were not significantly increased in PAH-PASMCs compared with non-PAH-PASMCs under hypoxia. Under normoxia, ATP production was significantly lower in PAH-PASMCs (59 ± 5 pmol/min) than in non-PAH-PASMCs (70 ± 10 pmol/min). On the other hand, ATP production was significantly higher in PAH-PASMCs (31 ± 5 pmol/min) than in non-PAH-PASMCs (14 ± 3 pmol/min) under hypoxia. Conclusions: There is an underlying change in the metabolic strategy to generate ATP production under the challenge of hypoxia.

    DOI: 10.3390/jcm12155028

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  • Microcalcification and 99mTc-Pyrophosphate Uptake without Increased Bone Metabolism in Cardiac Tissue from Patients with Transthyretin Cardiac Amyloidosis

    Atsushi Mori, Yukihiro Saito, Kazufumi Nakamura, Toshihiro Iida, Satoshi Akagi, Masashi Yoshida, Makiko Taniyama, Toru Miyoshi, Hiroshi Ito

    International Journal of Molecular Sciences   24 ( 3 )   1921 - 1921   2023年1月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    Transthyretin cardiac amyloidosis (ATTR-CA) is characterized by high 99mTc-labeled bone tracer uptake in the heart. However, the mechanism of bone tracer uptake into the heart remains controversial. Since bone tracer uptake into metastatic bone tumors is thought to be associated with increased bone metabolism, we examined 99mTc-pyrophosphate (PYP) scintigraphy findings, endomyocardial biopsy (EMB) tissue findings, and the expression of bone metabolism-related genes in the EMB tissues in patients with ATTR-CA, amyloid light-chain cardiac amyloidosis (AL-CA), and noncardiac amyloidosis (non-CA) in this study. The uptake of 99mTc-PYP in the heart was significantly higher in the ATTR-CA patients than in the AL-CA and non-CA patients. A higher percentage of ATTR-CA EMB tissue showed von Kossa-positive microparticles: ATTR-CA, 62%; AL-CA, 33%; and non-CA, 0%. Calcified microparticles were identified using transmission electron microscopy. However, none of the osteogenic marker genes, osteoclastic marker genes, or phosphate/pyrophosphate-related genes were upregulated in the EMB samples from ATTR-CA patients compared to those from AL-CA and non-CA patients. These results suggest that active calcification-promoting mechanisms are not involved in the microcalcification observed in the heart in ATTR-CA. The mechanisms explaining bone tracer uptake in the heart, which is stronger than that in the ribs, require further investigation.

    DOI: 10.3390/ijms24031921

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  • Cilostazol Attenuates AngII-Induced Cardiac Fibrosis in apoE Deficient Mice

    Yoshiko Hada, Haruhito A. Uchida, Ryoko Umebayashi, Masashi Yoshida, Jun Wada

    International Journal of Molecular Sciences   23 ( 16 )   9065 - 9065   2022年8月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    Cardiac fibrosis is characterized by the net accumulation of extracellular matrix in the myocardium and is an integral component of most pathological cardiac conditions. Cilostazol, a selective inhibitor of phosphodiesterase type III with anti-platelet, anti-mitogenic, and vasodilating properties, is widely used to treat the ischemic symptoms of peripheral vascular disease. Here, we investigated whether cilostazol has a protective effect against Angiotensin II (AngII)-induced cardiac fibrosis. Male apolipoprotein E-deficient mice were fed either a normal diet or a diet containing cilostazol (0.1% wt/wt). After 1 week of diet consumption, the mice were infused with saline or AngII (1000 ng kg−1 min−1) for 28 days. AngII infusion increased heart/body weight ratio (p < 0.05), perivascular fibrosis (p < 0.05), and interstitial cardiac fibrosis (p < 0.0001), but were significantly attenuated by cilostazol treatment (p < 0.05, respectively). Cilostazol also reduced AngII-induced increases in fibrotic and inflammatory gene expression (p < 0.05, respectively). Furthermore, cilostazol attenuated both protein and mRNA abundance of osteopontin induced by AngII in vivo. In cultured human cardiac myocytes, cilostazol reduced mRNA expression of AngII-induced osteopontin in dose-dependent manner. This reduction was mimicked by forskolin treatment but was cancelled by co-treatment of H-89. Cilostazol attenuates AngII-induced cardiac fibrosis in mice through activation of the cAMP–PKA pathway.

    DOI: 10.3390/ijms23169065

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  • Pemafibrate Prevents Rupture of Angiotensin II-Induced Abdominal Aortic Aneurysms

    Naofumi Amioka, Toru Miyoshi, Tomoko Yonezawa, Megumi Kondo, Satoshi Akagi, Masashi Yoshida, Yukihiro Saito, Kazufumi Nakamura, Hiroshi Ito

    Frontiers in Cardiovascular Medicine   9   2022年6月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Frontiers Media SA  

    Background

    Abdominal aortic aneurysm (AAA) is a life-threatening disease that lacks effective preventive therapies. This study aimed to evaluate the effect of pemafibrate, a selective peroxisome proliferator-activated receptor alpha (PPARα) agonist, on AAA formation and rupture.

    Methods

    Experimental AAA was induced by subcutaneous angiotensin II (AngII) infusion in ApoE/ mice for 4 weeks. Pemafibrate (0.1 mg/kg/day) was administered orally. Dihydroethidium staining was used to evaluate the reactive oxygen species (ROS).

    Results

    The size of the AngII-induced AAA did not differ between pemafibrate- and vehicle-treated groups. However, a decreased mortality rate due to AAA rupture was observed in pemafibrate-treated mice. Pemafibrate ameliorated AngII-induced ROS and reduced the mRNA expression of interleukin-6 and tumor necrosis factor-α in the aortic wall. Gelatin zymography analysis demonstrated significant inhibition of matrix metalloproteinase-2 activity by pemafibrate. AngII-induced ROS production in human vascular smooth muscle cells was inhibited by pre-treatment with pemafibrate and was accompanied by an increase in catalase activity. Small interfering RNA-mediated knockdown of catalase or PPARα significantly attenuated the anti-oxidative effect of pemafibrate.

    Conclusion

    Pemafibrate prevented AAA rupture in a murine model, concomitant with reduced ROS, inflammation, and extracellular matrix degradation in the aortic wall. The protective effect against AAA rupture was partly mediated by the anti-oxidative effect of catalase induced by pemafibrate in the smooth muscle cells.

    DOI: 10.3389/fcvm.2022.904215

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  • Impact of shear wave dispersion slope analysis for assessing the severity of myocarditis

    Naofumi Amioka, Yoichi Takaya, Kazufumi Nakamura, Megumi Kondo, Kaoru Akazawa, Yuko Ohno, Keishi Ichikawa, Rie Nakayama, Yukihiro Saito, Satoshi Akagi, Toru Miyoshi, Masashi Yoshida, Hiroshi Morita, Hiroshi Ito

    Scientific Reports   12 ( 1 )   2022年5月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    Abstract

    This study aimed to elucidate the utility of a novel ultrasound-based technique, shear wave dispersion slope (SWDS) analysis, which estimates tissue viscosity, for evaluating the severity of myocardial inflammation. Experimental autoimmune myocarditis (EAM) at different disease phases [3-week (acute phase): n = 10, 5-week (subacute phase): n = 9, and 7-week (late phase): n = 11] were developed in male Lewis rats. SWDS was measured in the right and the left ventricular free walls (RVFW and LVFW) under a retrograde perfusion condition. Histological myocardial inflammation was evaluated by CD68 staining. The accumulation of CD68-positive cells was severe in the myocardium of the EAM 3-week group. The median (interquartile range) SWDS of RVFW was significantly higher in the EAM 3-week group [9.9 (6.5–11.0) m/s/kHz] than in the control group [5.4 (4.5–6.8) m/s/kHz] (P = 0.034). The median SWDS of LVFW was also significantly higher in the EAM 3-week group [8.1 (6.4–11.0) m/s/kHz] than in the control group [4.4 (4.2–4.8) m/s/kHz] (P = 0.003). SWDS and the percentage of CD68-positive area showed a significant correlation in RVFW (R2 = 0.64, P < 0.001) and LVFW (R2 = 0.73, P < 0.001). This study showed that SWDS was elevated in ventricular walls with acute inflammation and also significantly correlated with the degree of myocardial inflammation. These results suggest the potential of SWDS in estimating the histological severity of acute myocarditis.

    DOI: 10.1038/s41598-022-12935-6

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    その他リンク: https://www.nature.com/articles/s41598-022-12935-6

  • Enhancement of pacing function by HCN4 overexpression in human pluripotent stem cell-derived cardiomyocytes

    Yukihiro Saito, Kazufumi Nakamura, Masashi Yoshida, Hiroki Sugiyama, Satoshi Akagi, Toru Miyoshi, Hiroshi Morita, Hiroshi Ito

    Stem Cell Research & Therapy   13 ( 1 )   2022年4月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    Abstract

    Background

    The number of patients with bradyarrhythmia and the number of patients with cardiac pacemakers are increasing with the aging population and the increase in the number of patients with heart diseases. Some patients in whom a cardiac pacemaker has been implanted experience problems such as pacemaker infection and inconvenience due to electromagnetic interference. We have reported that overexpression of HCN channels producing a pacemaker current in mouse embryonic stem cell-derived cardiomyocytes showed enhanced pacing function in vitro and in vivo. The aim of this study was to determine whether HCN4 overexpression in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) can strengthen the pacing function of the cells.

    Methods

    Human HCN4 was transduced in the AAVS1 locus of human induced pluripotent stem cells by nucleofection and HCN4-overexpressing iPSC-CMs were generated. Gene expression profiles, frequencies of spontaneous contraction and pacing abilities of HCN4-overexpressing and non-overexpressing iPSC-CMs in vitro were compared.

    Results

    HCN4-overexpressing iPSC-CMs showed higher spontaneous contraction rates than those of non-overexpressing iPSC-CMs. They responded to an HCN channel blocker and β adrenergic stimulation. The pacing rates against parent iPSC line-derived cardiomyocytes were also higher in HCN4-overexpressing iPSC-CMs than in non-overexpressing iPSC-CMs.

    Conclusions

    Overexpression of HCN4 showed enhancement of If current, spontaneous firing and pacing function in iPSC-CMs. These data suggest this transgenic cell line may be useful as a cardiac pacemaker.

    DOI: 10.1186/s13287-022-02818-y

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    その他リンク: https://link.springer.com/article/10.1186/s13287-022-02818-y/fulltext.html

  • Pathophysiology and Treatment of Diabetic Cardiomyopathy and Heart Failure in Patients with Diabetes Mellitus

    Kazufumi Nakamura, Toru Miyoshi, Masashi Yoshida, Satoshi Akagi, Yukihiro Saito, Kentaro Ejiri, Naoaki Matsuo, Keishi Ichikawa, Keiichiro Iwasaki, Takanori Naito, Yusuke Namba, Masatoki Yoshida, Hiroki Sugiyama, Hiroshi Ito

    International Journal of Molecular Sciences   23 ( 7 )   3587 - 3587   2022年3月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    There is a close relationship between diabetes mellitus and heart failure, and diabetes is an independent risk factor for heart failure. Diabetes and heart failure are linked by not only the complication of ischemic heart disease, but also by metabolic disorders such as glucose toxicity and lipotoxicity based on insulin resistance. Cardiac dysfunction in the absence of coronary artery disease, hypertension, and valvular disease is called diabetic cardiomyopathy. Diabetes-induced hyperglycemia and hyperinsulinemia lead to capillary damage, myocardial fibrosis, and myocardial hypertrophy with mitochondrial dysfunction. Lipotoxicity with extensive fat deposits or lipid droplets is observed on cardiomyocytes. Furthermore, increased oxidative stress and inflammation cause cardiac fibrosis and hypertrophy. Treatment with a sodium glucose cotransporter 2 (SGLT2) inhibitor is currently one of the most effective treatments for heart failure associated with diabetes. However, an effective treatment for lipotoxicity of the myocardium has not yet been established, and the establishment of an effective treatment is needed in the future. This review provides an overview of heart failure in diabetic patients for the clinical practice of clinicians.

    DOI: 10.3390/ijms23073587

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  • LCZ696 ameliorates doxorubicin-induced cardiomyocyte toxicity in rats

    Toru Miyoshi, Kazufumi Nakamura, Naofumi Amioka, Omer F. Hatipoglu, Tomoko Yonezawa, Yukihiro Saito, Masashi Yoshida, Satoshi Akagi, Hiroshi Ito

    Scientific Reports   12 ( 1 )   2022年3月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    Abstract

    Doxorubicin (DOX)-based chemotherapy induces cardiotoxicity, which is considered the main bottleneck for its clinical application. In this study, we investigated the potential benefit of LCZ696, an angiotensin receptor–neprilysin inhibitor against DOX-induced cardiotoxicity in rats and H9c2 cells and determined whether the mechanism underlying any such effects involves its antioxidant activity. Male Sprague–Dawley rats were randomly separated into four groups, each consisting of 15 rats (DOX (1.5 mg/kg/day intraperitoneally for 10 days followed by non-treatment for 8 days); DOX + valsartan (31 mg/kg/day by gavage from day 1 to day 18); DOX + LCZ696 (68 mg/kg/day by gavage from day 1 to day 18); and control (saline intraperitoneally for 10 days). DOX-induced elevation of cardiac troponin T levels on day 18 was significantly reduced by LCZ696, but not valsartan. The DOX-induced increase in myocardial reactive oxygen species (ROS) levels determined using dihydroethidium was significantly ameliorated by LCZ696, but not valsartan, and was accompanied by the suppression of DOX-induced increase in p47phox. LCZ696 recovered the DOX-induced decrease in phosphorylation of adenosine monophosphate-activated protein kinase and increased the ratio of Bax and Bcl-2. In H9c2 cardiomyocytes, LCZ696 reduced DOX-induced mitochondrial ROS generation and improved cell viability more than valsartan. Our findings indicated that LCZ696 ameliorated DOX-induced cardiotoxicity in rat hearts in vivo and in vitro, possibly by mediating a decrease in oxidative stress.

    DOI: 10.1038/s41598-022-09094-z

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    その他リンク: https://www.nature.com/articles/s41598-022-09094-z

  • Fragmented QRS as a predictor of cardiac events in patients with cardiac sarcoidosis

    Soichiro Ogura, Kazufumi Nakamura, Hiroshi Morita, Koji Nakagawa, Nobuhiro Nishii, Satoshi Akagi, Norihisa Toh, Yoichi Takaya, Masashi Yoshida, Toru Miyoshi, Atsuyuki Watanabe, Hiroshi Ito

    Journal of Cardiology   79 ( 3 )   446 - 452   2022年3月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.jjcc.2021.10.022

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  • Efficacy of shear wave elasticity for evaluating myocardial hypertrophy in hypertensive rats

    Yoichi Takaya, Kazufumi Nakamura, Rie Nakayama, Hiroaki Ohtsuka, Naofumi Amioka, Megumi Kondo, Kaoru Akazawa, Yuko Ohno, Keishi Ichikawa, Yukihiro Saito, Satoshi Akagi, Masashi Yoshida, Toru Miyoshi, Hiroshi Ito

    Scientific Reports   11 ( 1 )   2021年11月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    Abstract

    Shear wave (SW) imaging is a novel ultrasound-based technique for assessing tissue characteristics. SW elasticity may be useful to assess the severity of hypertensive left ventricular (LV) hypertrophy. This study aimed to evaluate the efficacy of SW elasticity for assessing the degree of myocardial hypertrophy using hypertensive rats. Rats were divided into hypertension group and control group. SW elasticity was measured on the excised heart. Myocardial hypertrophy was assessed histologically. LV weight was greater in hypertension group. An increase in interventricular septum and LV free wall thicknesses was observed in hypertension group. SW elasticity was significantly higher in hypertension group than in control group (14.6 ± 4.3 kPa vs. 6.5 ± 1.1 kPa, P < 0.01). The cross-sectional area of cardiomyocytes was larger in hypertension group than in control group (397 ± 50 μm2 vs. 243 ± 14 μm2, P < 0.01), and SW elasticity was positively correlated with the cross-sectional area of cardiomyocytes (R = 0.96, P < 0.01). This study showed that SW elasticity was higher in hypertensive rats and was closely correlated with the degree of myocardial hypertrophy, suggesting the efficacy of SW elasticity for estimating the severity of hypertensive LV hypertrophy.

    DOI: 10.1038/s41598-021-02271-6

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    その他リンク: https://www.nature.com/articles/s41598-021-02271-6

  • Preventative effects of bisoprolol transdermal patches on postoperative atrial fibrillation in high-risk patients undergoing non-cardiac surgery: A subanalysis of the MAMACARI study

    Takayuki Iwano, Hironobu Toda, Kazufumi Nakamura, Kazuyoshi Shimizu, Kentaro Ejiri, Yoichiro Naito, Hisatoshi Mori, Takuro Masuda, Toru Miyoshi, Masashi Yoshida, Yukiko Hikasa, Hiroshi Morimatsu, Hiroshi Ito

    Journal of Cardiology   78 ( 5 )   349 - 354   2021年11月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.jjcc.2021.05.001

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  • Pathological and clinical effects of interleukin-6 on human myocarditis

    Naofumi Amioka, Kazufumi Nakamura, Tomonari Kimura, Keiko Ohta-Ogo, Takehiro Tanaka, Tomohiro Toji, Satoshi Akagi, Koji Nakagawa, Norihisa Toh, Masashi Yoshida, Toru Miyoshi, Nobuhiro Nishii, Atsuyuki Watanabe, Ryotaro Asano, Takeshi Ogo, Yoshikazu Nakaoka, Hiroshi Morita, Hiroyuki Yanai, Hiroshi Ito

    Journal of Cardiology   78 ( 2 )   157 - 165   2021年8月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.jjcc.2021.03.003

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  • Incremental prognostic value of non-alcoholic fatty liver disease over coronary computed tomography angiography findings in patients with suspected coronary artery disease

    Keishi Ichikawa, Toru Miyoshi, Kazuhiro Osawa, Takashi Miki, Hironobu Toda, Kentaro Ejiri, Masashi Yoshida, Kazufumi Nakamura, Hiroshi Morita, Hiroshi Ito

    European Journal of Preventive Cardiology   28 ( 18 )   2059 - 2066   2021年7月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Oxford University Press (OUP)  

    Abstract

    Aims

    This study aimed to investigate additional risk stratification benefits of hepatic steatosis (HS) concurrently assessed during coronary computed tomography angiography (CTA) in a large patient cohort with suspected stable coronary artery disease (CAD).

    Methods and results

    In this prospective study, 1148 Japanese outpatients without a history of CAD who underwent coronary CTA for suspected stable CAD (mean age 64 ± 14 years) were included. HS, defined on CT as a hepatic-to-spleen attenuation ratio of <1.0, was examined just before the evaluation of adverse CTA findings, defined as obstructive and/or high-risk plaque. The major adverse cardiac events (MACE) were the composite of cardiac death, acute coronary syndrome, and late revascularization. The incremental predictive value of HS was evaluated using the global χ2 test and C-statistic. HS was identified in 247 (22%) patients. During a median follow-up of 3.9 years, MACE was observed in 40 (3.5%) patients. HS was significantly associated with MACE in a model that included adverse CTA findings (hazard ratio 4.01, 95% confidence interval 2.12–7.59, P < 0.001). By adding HS to the Framingham risk score and adverse CTA findings, the global χ2 score and C-statistic significantly increased from 29.0 to 49.5 (P < 0.001) and 0.74 to 0.81 (P = 0.026), respectively. In subgroup analyses in patients with diabetes mellitus and metabolic syndrome, HS had significant additive predictive value for MACE over the Framingham risk score and adverse CTA findings.

    Conclusion

    In patients with suspected stable CAD, concurrent evaluation of HS during coronary CTA enables more accurate detection of patients at higher risk of MACE.

    DOI: 10.1093/eurjpc/zwab120

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  • Efficacy of shear wave elastography for evaluating right ventricular myocardial fibrosis in monocrotaline-induced pulmonary hypertension rats

    Rie Nakayama, Yoichi Takaya, Kazufumi Nakamura, Megumi Kondo, Kaoru Kobayashi, Yuko Ohno, Naofumi Amioka, Satoshi Akagi, Masashi Yoshida, Toru Miyoshi, Hiroshi Ito

    Journal of Cardiology   78 ( 1 )   17 - 23   2021年7月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.jjcc.2021.01.015

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  • Inhibitory effects of RAGE-aptamer on development of monocrotaline-induced pulmonary arterial hypertension in rats

    Kazufumi Nakamura, Satoshi Akagi, Kentaro Ejiri, Masashi Yoshida, Toru Miyoshi, Masakiyo Sakaguchi, Naofumi Amioka, Luh Oliva Saraswati Suastika, Megumi Kondo, Rie Nakayama, Yoichi Takaya, Yuichiro Higashimoto, Kei Fukami, Hiromi Matsubara, Hiroshi Ito

    Journal of Cardiology   78 ( 1 )   12 - 16   2021年7月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.jjcc.2020.12.009

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  • Prognostic value of non-alcoholic fatty liver disease for predicting cardiovascular events in patients with diabetes mellitus with suspected coronary artery disease: a prospective cohort study

    Keishi Ichikawa, Toru Miyoshi, Kazuhiro Osawa, Takashi Miki, Hironobu Toda, Kentaro Ejiri, Masatoki Yoshida, Yusuke Nanba, Masashi Yoshida, Kazufumi Nakamura, Hiroshi Morita, Hiroshi Ito

    Cardiovascular Diabetology   20 ( 1 )   2021年1月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    Abstract

    Background

    Risk stratification of cardiovascular events in patients with type 2 diabetes mellitus (T2DM) has not been established. Coronary artery calcium score (CACS) and non-alcoholic fatty liver disease (NAFLD) are independently associated with cardiovascular events in T2DM patients. This study examined the incremental prognostic value of NAFLD assessed by non-enhanced computed tomography (CT) in addition to CACS and Framingham risk score (FRS) for cardiovascular events in T2DM patients.

    Methods

    This prospective pilot study included 529 T2DM outpatients with no history of cardiovascular disease who underwent CACS measurement because of suspected coronary artery disease. NAFLD was defined on CT images as a liver:spleen attenuation ratio < 1.0. Cardiovascular events were defined as cardiovascular death, nonfatal myocardial infarction, late coronary revascularization, nonfatal stroke, or hospitalization for heart failure.

    Results

    Among 529 patients (61% men, mean age 65 years), NAFLD was identified in 143 (27%). Forty-four cardiovascular events were documented during a median follow-up of 4.4 years. In multivariate Cox regression analysis, NAFLD, CACS, and FRS were associated with cardiovascular events (hazard ratios and 95% confidence intervals 5.43, 2.82–10.44, p < 0.001; 1.56, 1.32–1.86, p < 0.001; 1.23, 1.08–1.39, p = 0.001, respectively). The global χ2 score for predicting cardiovascular events increased significantly from 27.0 to 49.7 by adding NAFLD to CACS and FRS (p < 0.001). The addition of NAFLD to a model including CACS and FRS significantly increased the C-statistic from 0.71 to 0.80 (p = 0.005). The net reclassification achieved by adding CACS and FRS was 0.551 (p < 0.001).

    Conclusions

    NAFLD assessed by CT, in addition to CACS and FRS, could be useful for identifying T2DM patients at higher risk of cardiovascular events.

    DOI: 10.1186/s12933-020-01192-4

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    その他リンク: http://link.springer.com/article/10.1186/s12933-020-01192-4/fulltext.html

  • Inhibition of interleukin-6 signaling attenuates aortitis, left ventricular hypertrophy and arthritis in interleukin-1 receptor antagonist deficient mice

    Yoshiko Hada, Haruhito A. Uchida, Tomoyuki Mukai, Fumiaki Kojima, Masashi Yoshida, Hidemi Takeuchi, Yuki Kakio, Nozomu Otaka, Yoshitaka Morita, Jun Wada

    Clinical Science   134 ( 20 )   2771 - 2787   2020年10月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Portland Press Ltd.  

    Abstract

    The aim of the present study was to examine whether inhibition of Interleukin (IL)-6 signaling by MR16-1, an IL-6 receptor antibody, attenuates aortitis, cardiac hypertrophy, and arthritis in IL-1 receptor antagonist deficient (IL-1RA KO) mice. Four weeks old mice were intraperitoneally administered with either MR16-1 or non-immune IgG at dosages that were adjusted over time for 5 weeks. These mice were stratified into four groups: MR16-1 treatment groups, KO/MR low group (first 2.0 mg, following 0.5 mg/week, n=14) and KO/MR high group (first 4.0 mg, following 2.0 mg/week, n=19) in IL-1RA KO mice, and IgG treatment groups, KO/IgG group (first 2.0 mg, following 1.0 mg/week, n=22) in IL-1RA KO mice, and wild/IgG group (first 2.0 mg, following 1.0 mg/week, n=17) in wild mice. Aortitis, cardiac hypertrophy and arthropathy were histologically analyzed. Sixty-eight percent of the KO/IgG group developed aortitis (53% developed severe aortitis). In contrast, only 21% of the KO/MR high group developed mild aortitis, without severe aortitis (P<0.01, vs KO/IgG group). Infiltration of inflammatory cells, such as neutrophils, T cells, and macrophages, was frequently observed around aortic sinus of the KO/IgG group. Left ventricle and cardiomyocyte hypertrophy were observed in IL-1RA KO mice. Administration of high dosage of MR16-1 significantly suppressed cardiomyocyte hypertrophy. MR16-1 attenuated the incidence and severity of arthritis in IL-1RA KO mice in a dose-dependent manner. In conclusion, blockade of IL-6 signaling may exert a beneficial effect to attenuate severe aortitis, left ventricle hypertrophy, and arthritis.

    DOI: 10.1042/cs20201036

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  • Combination therapy with pemafibrate (K-877) and pitavastatin improves vascular endothelial dysfunction in dahl/salt-sensitive rats fed a high-salt and high-fat diet

    Masatoki Yoshida, Kazufumi Nakamura, Toru Miyoshi, Masashi Yoshida, Megumi Kondo, Kaoru Akazawa, Tomonari Kimura, Hiroaki Ohtsuka, Yuko Ohno, Daiji Miura, Hiroshi Ito

    Cardiovascular Diabetology   19 ( 1 )   2020年9月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    Abstract

    Background

    Statins suppress the progression of atherosclerosis by reducing low-density lipoprotein (LDL) cholesterol levels. Pemafibrate (K-877), a novel selective peroxisome proliferator-activated receptor α modulator, is expected to reduce residual risk factors including high triglycerides (TGs) and low high-density lipoprotein (HDL) cholesterol during statin treatment. However, it is not known if statin therapy with add-on pemafibrate improves the progression of atherosclerosis. The aim of this study was to assess the effect of combination therapy with pitavastatin and pemafibrate on lipid profiles and endothelial dysfunction in hypertension and insulin resistance model rats.

    Methods

    Seven-week-old male Dahl salt-sensitive (DS) rats were divided into the following five treatment groups (normal diet (ND) plus vehicle, high-salt and high-fat diet (HD) plus vehicle, HD plus pitavastatin (0.3 mg/kg/day), HD plus pemafibrate (K-877) (0.5 mg/kg/day), and HD plus combination of pitavastatin and pemafibrate) and treated for 12 weeks. At 19 weeks, endothelium-dependent relaxation of the thoracic aorta in response to acetylcholine was evaluated.

    Results

    After feeding for 12 weeks, systolic blood pressure and plasma levels of total cholesterol were significantly higher in the HD-vehicle group compared with the ND-vehicle group. Combination therapy with pitavastatin and pemafibrate significantly reduced systolic blood pressure, TG levels, including total, chylomicron (CM), very LDL (VLDL), HDL-TG, and cholesterol levels, including total, CM, VLDL, and LDL-cholesterol, compared with vehicle treatment. Acetylcholine caused concentration-dependent relaxation of thoracic aorta rings that were pre-contracted with phenylephrine in all rats. Relaxation rates in the HD-vehicle group were significantly lower compared with the ND-vehicle group. Relaxation rates in the HD-combination of pitavastatin and pemafibrate group significantly increased compared with the HD-vehicle group, although neither medication alone ameliorated relaxation rates significantly. Western blotting experiments showed increased phosphorylated endothelial nitric oxide synthase protein expression in aortas from rats in the HD-pemafibrate group and the HD-combination group compared with the HD-vehicle group. However, the expression levels did not respond significantly to pitavastatin alone.

    Conclusions

    Combination therapy with pitavastatin and pemafibrate improved lipid profiles and endothelial dysfunction in hypertension and insulin resistance model rats. Pemafibrate as an add-on strategy to statins may be useful for preventing atherosclerosis progression.

    DOI: 10.1186/s12933-020-01132-2

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    その他リンク: https://link.springer.com/article/10.1186/s12933-020-01132-2/fulltext.html

  • Chemoradiation therapy for non-small cell lung cancer exacerbates thoracic aortic calcification determined by computed tomography

    Takashi Miki, Shunsaku Miyauchi, Toru Miyoshi, Masashi Yoshida, Keishi Ichikawa, Junichi Soh, Kazufumi Nakamura, Katsuyuki Kiura, Susumu Kanazawa, Shinichi Toyooka, Hiroshi Ito

    Heart and Vessels   35 ( 10 )   1401 - 1408   2020年4月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    DOI: 10.1007/s00380-020-01611-2

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    その他リンク: https://link.springer.com/article/10.1007/s00380-020-01611-2/fulltext.html

  • Deficiency of CD44 prevents thoracic aortic dissection in a murine model

    Omer F. Hatipoglu, Toru Miyoshi, Tomoko Yonezawa, Megumi Kondo, Naofumi Amioka, Masashi Yoshida, Satoshi Akagi, Kazufumi Nakamura, Satoshi Hirohata, Hiroshi Ito

    Scientific Reports   10 ( 1 )   2020年4月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    Abstract

    Thoracic aortic dissection (TAD) is a life-threatening vascular disease. We showed that CD44, a widely distributed cell surface adhesion molecule, has an important role in inflammation. In this study, we examined the role of CD44 in the development of TAD. TAD was induced by the continuous infusion of β-aminopropionitrile (BAPN), a lysyl oxidase inhibitor, and angiotensin II (AngII) for 7 days in wild type (WT) mice and CD44 deficient (CD44-/-) mice. The incidence of TAD in CD44-/- mice was significantly reduced compared with WT mice (44% and 6%, p < 0.01). Next, to evaluate the initial changes, aortic tissues at 24 hours after BAPN/AngII infusion were examined. Neutrophil accumulation into thoracic aortic adventitia in CD44-/- mice was significantly decreased compared with that in WT mice (5.7 ± 0.3% and 1.6 ± 0.4%, p < 0.01). In addition, BAPN/AngII induced interleukin-6, interleukin-1β, matrix metalloproteinase-2 and matrix metalloproteinase-9 in WT mice, all of which were significantly reduced in CD44−/− mice (all p < 0.01). In vitro transmigration of neutrophils from CD44−/− mice through an endothelial monolayer was significantly decreased by 18% compared with WT mice (p < 0.01). Our findings indicate that CD44 has a critical role in TAD development in association with neutrophil infiltration into adventitia.

    DOI: 10.1038/s41598-020-63824-9

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    その他リンク: https://www.nature.com/articles/s41598-020-63824-9

  • Effects of Bisoprolol Transdermal Patches for Prevention of Perioperative Myocardial Injury in High-Risk Patients Undergoing Non-Cardiac Surgery ― Multicenter Randomized Controlled Study ―

    Hironobu Toda, Kazufumi Nakamura, Kazuyoshi Shimizu, Kentaro Ejiri, Takayuki Iwano, Toru Miyoshi, Koji Nakagawa, Masashi Yoshida, Atsuyuki Watanabe, Nobuhiro Nishii, Yukiko Hikasa, Masao Hayashi, Hiroshi Morita, Hiroshi Morimatsu, Hiroshi Ito

    Circulation Journal   84 ( 4 )   642 - 649   2020年3月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Circulation Society  

    DOI: 10.1253/circj.cj-19-0871

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  • New Appearance of Fragmented QRS as a Predictor of Ventricular Arrhythmic Events in Patients With Hypertrophic Cardiomyopathy

    Soichiro Ogura, Kazufumi Nakamura, Hiroshi Morita, Norihisa Toh, Koji Nakagawa, Masashi Yoshida, Atsuyuki Watanabe, Nobuhiro Nishii, Toru Miyoshi, Hiroshi Ito

    Circulation Journal   84 ( 3 )   487 - 494   2020年2月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Circulation Society  

    DOI: 10.1253/circj.cj-19-0968

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  • Low Consultation Rate of General Population with Atrial Fibrillation

    Hiroaki Matsumi, Kazufumi Nakamura, Eri Eguchi, Toru Miyoshi, Koji Nakagawa, Nobuhiro Nishii, Atsuyuki Watanabe, Akira Ueoka, Masashi Yoshida, Naoto Tokunaga, Naofumi Amioka, Nobuyuki Yamada, Daiji Saito, Hiroshi Morita, Keiki Ogino, Hiroshi Ito

    International Heart Journal   60 ( 6 )   1303 - 1307   2019年11月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:International Heart Journal (Japanese Heart Journal)  

    DOI: 10.1536/ihj.19-062

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  • Current Treatment Strategies and Nanoparticle-Mediated Drug Delivery Systems for Pulmonary Arterial Hypertension

    Kazufumi Nakamura, Satoshi Akagi, Kentaro Ejiri, Masashi Yoshida, Toru Miyoshi, Norihisa Toh, Koji Nakagawa, Yoichi Takaya, Hiromi Matsubara, Hiroshi Ito

    International Journal of Molecular Sciences   20 ( 23 )   5885 - 5885   2019年11月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    There are three critical pathways for the pathogenesis and progression of pulmonary arterial hypertension (PAH): the prostacyclin (prostaglandin I2) (PGI2), nitric oxide (NO), and endothelin pathways. The current approved drugs targeting these three pathways, including prostacyclin (PGI2), phosphodiesterase type-5 (PDE5) inhibitors, and endothelin receptor antagonists (ERAs), have been shown to be effective, however, PAH remains a severe clinical condition and the long-term survival of patients with PAH is still suboptimal. The full therapeutic abilities of available drugs are reduced by medication, patient non-compliance, and side effects. Nanoparticles are expected to address these problems by providing a novel drug delivery approach for the treatment of PAH. Drug-loaded nanoparticles for local delivery can optimize the efficacy and minimize the adverse effects of drugs. Prostacyclin (PGI2) analogue, PDE5 inhibitors, ERA, pitavastatin, imatinib, rapamycin, fasudil, and oligonucleotides-loaded nanoparticles have been reported to be effective in animal PAH models and in vitro studies. However, the efficacy and safety of nanoparticle mediated-drug delivery systems for PAH treatment in humans are unknown and further clinical studies are required to clarify these points.

    DOI: 10.3390/ijms20235885

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  • Effect of LCZ696, a dual angiotensin receptor neprilysin inhibitor, on isoproterenol-induced cardiac hypertrophy, fibrosis, and hemodynamic change in rats

    Toru Miyoshi, Kazufumi Nakamura, Daiji Miura, Masashi Yoshida, Yukihiro Saito, Satoshi Akagi, Yuko Ohno, Megumi Kondo, Hiroshi Ito

    Cardiology Journal   26 ( 5 )   575 - 583   2019年11月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:VM Media SP. zo.o VM Group SK  

    DOI: 10.5603/cj.a2018.0048

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  • Emerging Role of Coronary Computed Tomography Angiography in Lipid-Lowering Therapy: a Bridge to Image-Guided Personalized Medicine

    Toru Miyoshi, Kazuhiro Osawa, Keishi Ichikawa, Kazuki Suruga, Takashi Miki, Masashi Yoshida, Koji Nakagawa, Hironobu Toda, Kazufumi Nakamura, Hiroshi Morita, Hiroshi Ito

    Current Cardiology Reports   21 ( 8 )   2019年6月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    DOI: 10.1007/s11886-019-1170-4

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    その他リンク: http://link.springer.com/article/10.1007/s11886-019-1170-4/fulltext.html

  • Inhibitory Effects of Tofogliflozin on Cardiac Hypertrophy in Dahl Salt-Sensitive and Salt-Resistant Rats Fed a High-Fat Diet

    Tomonari Kimura, Kazufumi Nakamura, Toru Miyoshi, Masashi Yoshida, Kaoru Akazawa, Yukihiro Saito, Satoshi Akagi, Yuko Ohno, Megumi Kondo, Daiji Miura, Jun Wada, Hiroshi Ito

    International Heart Journal   60 ( 3 )   728 - 735   2019年5月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:International Heart Journal (Japanese Heart Journal)  

    DOI: 10.1536/ihj.18-392

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  • Crucial role of RAGE in inappropriate increase of smooth muscle cells from patients with pulmonary arterial hypertension

    Kazufumi Nakamura, Masakiyo Sakaguchi, Hiromi Matsubara, Satoshi Akagi, Toshihiro Sarashina, Kentaro Ejiri, Kaoru Akazawa, Megumi Kondo, Koji Nakagawa, Masashi Yoshida, Toru Miyoshi, Takeshi Ogo, Takahiro Oto, Shinichi Toyooka, Yuichiro Higashimoto, Kei Fukami, Hiroshi Ito

    PLOS ONE   13 ( 9 )   e0203046 - e0203046   2018年9月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Public Library of Science (PLoS)  

    DOI: 10.1371/journal.pone.0203046

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  • HCN4-Overexpressing Mouse Embryonic Stem Cell-Derived Cardiomyocytes Generate a New Rapid Rhythm in Rats with Bradycardia

    Yukihiro Saito, Kazufumi Nakamura, Masashi Yoshida, Hiroki Sugiyama, Makoto Takano, Satoshi Nagase, Hiroshi Morita, Kengo F. Kusano, Hiroshi Ito

    International Heart Journal   59 ( 3 )   601 - 606   2018年5月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:International Heart Journal (Japanese Heart Journal)  

    DOI: 10.1536/ihj.17-241

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  • TRPM4 Mutation in Patients With Ventricular Noncompaction and Cardiac Conduction Disease

    Yukihiro Saito, Kazufumi Nakamura, Nobuhiro Nishi, Osamu Igawa, Masashi Yoshida, Toru Miyoshi, Atsuyuki Watanabe, Hiroshi Morita, Hiroshi Ito

    Circulation: Genomic and Precision Medicine   11 ( 5 )   2018年5月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Ovid Technologies (Wolters Kluwer Health)  

    DOI: 10.1161/circgen.118.002103

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  • Suppression of Wnt Signaling and Osteogenic Changes in Vascular Smooth Muscle Cells by Eicosapentaenoic Acid

    Yukihiro Saito, Kazufumi Nakamura, Daiji Miura, Kei Yunoki, Toru Miyoshi, Masashi Yoshida, Norifumi Kawakita, Tomonari Kimura, Megumi Kondo, Toshihiro Sarashina, Satoshi Akagi, Atsuyuki Watanabe, Nobuhiro Nishii, Hiroshi Morita, Hiroshi Ito

    Nutrients   9 ( 8 )   858 - 858   2017年8月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    DOI: 10.3390/nu9080858

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  • Eicosapentaenoic acid prevents arterial calcification in klotho mutant mice

    Kazufumi Nakamura, Daiji Miura, Yukihiro Saito, Kei Yunoki, Yasushi Koyama, Minoru Satoh, Megumi Kondo, Kazuhiro Osawa, Omer F. Hatipoglu, Toru Miyoshi, Masashi Yoshida, Hiroshi Morita, Hiroshi Ito

    PLOS ONE   12 ( 8 )   e0181009 - e0181009   2017年8月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Public Library of Science (PLoS)  

    DOI: 10.1371/journal.pone.0181009

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  • Nanoparticle-Mediated Drug Delivery System for Pulmonary Arterial Hypertension

    Kazufumi Nakamura, Hiromi Matsubara, Satoshi Akagi, Toshihiro Sarashina, Kentaro Ejiri, Norifumi Kawakita, Masashi Yoshida, Toru Miyoshi, Atsuyuki Watanabe, Nobuhiro Nishii, Hiroshi Ito

    Journal of Clinical Medicine   6 ( 5 )   48 - 48   2017年4月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    DOI: 10.3390/jcm6050048

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  • Enhancement of Spontaneous Activity by HCN4 Overexpression in Mouse Embryonic Stem Cell-Derived Cardiomyocytes - A Possible Biological Pacemaker

    Yukihiro Saito, Kazufumi Nakamura, Masashi Yoshida, Hiroki Sugiyama, Tohru Ohe, Junko Kurokawa, Tetsushi Furukawa, Makoto Takano, Satoshi Nagase, Hiroshi Morita, Kengo F. Kusano, Hiroshi Ito

    PLOS ONE   10 ( 9 )   e0138193 - e0138193   2015年9月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Public Library of Science (PLoS)  

    DOI: 10.1371/journal.pone.0138193

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  • Directed Differentiation of Patient-Specific Induced Pluripotent Stem Cells Identifies the Transcriptional Repression and Epigenetic Modification of NKX2-5, HAND1, and NOTCH1 in Hypoplastic Left Heart Syndrome

    Junko Kobayashi, Masashi Yoshida, Suguru Tarui, Masataka Hirata, Yusuke Nagai, Shingo Kasahara, Keiji Naruse, Hiroshi Ito, Shunji Sano, Hidemasa Oh

    PLoS ONE   9 ( 7 )   e102796 - e102796   2014年7月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Public Library of Science (PLoS)  

    DOI: 10.1371/journal.pone.0102796

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  • Effect of vildagliptin, a dipeptidyl peptidase 4 inhibitor, on cardiac hypertrophy induced by chronic beta-adrenergic stimulation in rats

    Toru Miyoshi, Kazufumi Nakamura, Masashi Yoshida, Daiji Miura, Hiroki Oe, Satoshi Akagi, Hiroki Sugiyama, Kaoru Akazawa, Tomoko Yonezawa, Jun Wada, Hiroshi Ito

    Cardiovascular Diabetology   13 ( 1 )   43 - 43   2014年

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    DOI: 10.1186/1475-2840-13-43

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  • Prostaglandin I2 induces apoptosis via upregulation of Fas ligand in pulmonary artery smooth muscle cells from patients with idiopathic pulmonary arterial hypertension

    Satoshi Akagi, Kazufumi Nakamura, Hiromi Matsubara, Kengo Fukushima Kusano, Noriyuki Kataoka, Takahiro Oto, Katsumasa Miyaji, Aya Miura, Aiko Ogawa, Masashi Yoshida, Hatsue Ueda-Ishibashi, Chikao Yutani, Hiroshi Ito

    International Journal of Cardiology   165 ( 3 )   499 - 505   2013年5月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.ijcard.2011.09.004

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  • Intermittent arm ischemia induces vasodilatation of the contralateral upper limb

    Kenki Enko, Kazufumi Nakamura, Kei Yunoki, Toru Miyoshi, Satoshi Akagi, Masashi Yoshida, Norihisa Toh, Mutsuko Sangawa, Nobuhiro Nishii, Satoshi Nagase, Kunihisa Kohno, Hiroshi Morita, Kengo F. Kusano, Hiroshi Ito

    The Journal of Physiological Sciences   61 ( 6 )   2011年9月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    DOI: 10.1007/s12576-011-0172-9

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    その他リンク: http://link.springer.com/article/10.1007/s12576-011-0172-9/fulltext.html

  • Increased Akt-mTOR Signaling in Lung Epithelium Is Associated with Respiratory Distress Syndrome in Mice

    Hiroyuki Ikeda, Ichiro Shiojima, Toru Oka, Masashi Yoshida, Koji Maemura, Kenneth Walsh, Takashi Igarashi, Issei Komuro

    Molecular and Cellular Biology   31 ( 5 )   1054 - 1065   2011年3月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Informa UK Limited  

    DOI: 10.1128/mcb.00732-10

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    その他リンク: https://www.tandfonline.com/doi/pdf/10.1128/MCB.00732-10

  • Chronic doxorubicin cardiotoxicity is mediated by oxidative DNA damage-ATM-p53-apoptosis pathway and attenuated by pitavastatin through the inhibition of Rac1 activity

    Masashi Yoshida, Ichiro Shiojima, Hiroyuki Ikeda, Issei Komuro

    Journal of Molecular and Cellular Cardiology   47 ( 5 )   698 - 705   2009年11月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.yjmcc.2009.07.024

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  • Interaction of myocardial insulin receptor and IGF receptor signaling in exercise-induced cardiac hypertrophy

    Hiroyuki Ikeda, Ichiro Shiojima, Yukako Ozasa, Masashi Yoshida, Martin Holzenberger, C. Ronald Kahn, Kenneth Walsh, Takashi Igarashi, E. Dale Abel, Issei Komuro

    Journal of Molecular and Cellular Cardiology   47 ( 5 )   664 - 675   2009年11月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.yjmcc.2009.08.028

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  • IGFBP-4 is an inhibitor of canonical Wnt signalling required for cardiogenesis

    Weidong Zhu, Ichiro Shiojima, Yuzuru Ito, Zhi Li, Hiroyuki Ikeda, Masashi Yoshida, Atsuhiko T. Naito, Jun-ichiro Nishi, Hiroo Ueno, Akihiro Umezawa, Tohru Minamino, Toshio Nagai, Akira Kikuchi, Makoto Asashima, Issei Komuro

    Nature   454 ( 7202 )   345 - 349   2008年7月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    DOI: 10.1038/nature07027

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    その他リンク: https://www.nature.com/articles/nature07027

  • Novel percutaneous catheter thrombectomy in acute massive pulmonary embolism: Rotational bidirectional thrombectomy (ROBOT)

    Masashi Yoshida, Ichiro Inoue, Takuji Kawagoe, Masaharu Ishihara, Yuji Shimatani, Satoshi Kurisu, Kengo Fukushima Kusano, Tohru Ohe

    Catheterization and Cardiovascular Interventions   68 ( 1 )   112 - 117   2006年6月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    Abstract

    Background: Although thrombolysis is a standard therapy in cases of pulmonary embolism (PE), fatal outcome is often observed. We designed and investigated the efficacy of a novel percutaneous catheter therapy, rotational bidirectional thrombectomy (ROBOT), for PE. Methods and Results: Eighteen patients with acute massive PE (Miller score ≥ 20) were included in this study. We separated them into two groups [group A (n = 10), thrombolysis; group B (n = 8): thrombolysis and ROBOT or ROBOT alone]. There was no difference in the hemodynamic indices between the groups at diagnosis. ROBOT was designed to fragment emboli by rotating a regular pigtail catheter. Three deaths occurred in group A because of hemodynamic impairment, but there was no death in group B. One day after treatment, systolic pulmonary artery pressure had decreased from 53 ± 8 to 30 ± 8 mm Hg (P < 0.05) in group B and from 54 ± 5 to 42 ± 19 mm Hg (NS) in group A. The hospitalization period in group B was shorter than that in group A (17 ± 6 vs. 27 ± 10 days, P < 0.05). Conclusion: ROBOT therapy results in a significant, rapid improvement in the hemodynamic situation and in a better outcome than conventional therapy in patients with acute massive pulmonary embolism. © 2006 Wiley‐Liss, Inc.

    DOI: 10.1002/ccd.20747

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  • Time Course of Electrocardiographic Changes in Patients With Tako-Tsubo Syndrome-Comparison With Acute Myocardial Infarction With Minimal Enzymatic Release-

    Satoshi Kurisu, Ichiro Inoue, Takuji Kawagoe, Masaharu Ishihara, Yuji Shimatani, Suji Nakamura, Masashi Yoshida, Naoya Mitsuba, Takaki Hata, Hikaru Sato

    Circulation Journal   68 ( 1 )   77 - 81   2004年

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Circulation Society  

    DOI: 10.1253/circj.68.77

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  • Impact of acute hyperglycemia on left ventricular function after reperfusion therapy in patients with a first anterior wall acute myocardial infarction

    Masaharu Ishihara, Ichiro Inoue, Takuji Kawagoe, Yuji Shimatani, Satoshi Kurisu, Kenji Nishioka, Takashi Umemura, Shuji Nakamura, Masashi Yoshida

    American Heart Journal   146 ( 4 )   674 - 678   2003年10月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/s0002-8703(03)00167-4

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  • Effect of acute hyperglycemia on the ischemic preconditioning effect of prodromal angina pectoris in patients with a first anterior wall acute myocardial infarction

    Masaharu Ishihara, Ichiro Inoue, Takuji Kawagoe, Yuji Shimatani, Satoshi Kurisu, Kenji Nishioka, Takashi Umemura, Shuji Nakamura, Masashi Yoshida

    The American Journal of Cardiology   92 ( 3 )   288 - 291   2003年8月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/s0002-9149(03)00627-1

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  • Myocardial perfusion and fatty acid metabolism in patients with tako-tsubo-like left ventricular dysfunction

    Satoshi Kurisu, Ichiro Inoue, Takuji Kawagoe, Masaharu Ishihara, Yuji Shimatani, Kenji Nishioka, Takashi Umemura, Suji Nakamura, Masashi Yoshida, Hikaru Sato

    Journal of the American College of Cardiology   41 ( 5 )   743 - 748   2003年3月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/s0735-1097(02)02924-8

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  • Effect of prodromal angina pectoris on altering the relation between time to reperfusion and outcomes after a first anterior wall acute myocardial infarction

    Masaharu Ishihara, Ichiro Inoue, Takuji Kawagoe, Yuji Shimatani, Satoshi Kurisu, Kenji Nishioka, Takashi Umemura, Shuji Nakamura, Masashi Yoshida

    The American Journal of Cardiology   91 ( 2 )   128 - 132   2003年1月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/s0002-9149(02)03096-5

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  • Effect of Intraaortic Balloon Pumping on Left Ventricular Function in Patients With Persistent ST Segment Elevation After Revascularization for Acute Myocardial Infarction.

    Satoshi Kurisu, Ichiro Inoue, Takuji Kawagoe, Masaharu Ishihara, Yuji Shimatani, Kenji Nishioka, Takashi Umemura, Suji Nakamura, Masashi Yoshida

    Circulation Journal   67 ( 1 )   35 - 39   2003年

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Circulation Society  

    DOI: 10.1253/circj.67.35

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  • Left Ventricular Apical Thrombus Formation in a Patient With Suspected Tako-Tsubo-Like Left Ventricular Dysfunction

    Satoshi Kurisu, Ichiro Inoue, Takuji Kawagoe, Masaharu Ishihara, Yuji Shimatani, Kenji Nishioka, Takashi Umemura, Suji Nakamura, Masashi Yoshida, Hikaru Sato

    Circulation Journal   67 ( 6 )   556 - 558   2003年

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Circulation Society  

    DOI: 10.1253/circj.67.556

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  • Usefulness of Massive Oral Nicorandil in a Patient with Variant Angina Refractory to Conventional Treatment.

    Satoshi KURISU, Ichiro INOUE, Takuji KAWAGOE, Masaharu ISHIHARA, Yuji SHIMATANI, Kenji NISHIOKA, Shuji NAKAMURA, Takashi UMEMURA, Masashi YOSHIDA

    Internal Medicine   42 ( 2 )   163 - 167   2003年

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Society of Internal Medicine  

    DOI: 10.2169/internalmedicine.42.163

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  • Diabetes Mellitus is Associated with Insufficient Microvascular Reperfusion following Revascularization for Anterior Acute Myocardial Infarction

    Satoshi KURISU, Ichiro INOUE, Takuji KAWAGOE, Masaharu ISHIHARA, Yuji SHIMATANI, Kenji NisraoKA, Takashi UMEMURA, Suji NAKAMURA, Masashi YOSHIDA

    Internal Medicine   42 ( 7 )   554 - 559   2003年

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Society of Internal Medicine  

    DOI: 10.2169/internalmedicine.42.554

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  • Impact of spontaneous anterograde flow of the infarct artery on left ventricular function in patients with a first anterior wall acute myocardial infarction

    Masaharu Ishihara, Ichiro Inoue, Takuji Kawagoe, Yuji Shimatani, Satoshi Kurisu, Kenji Nishioka, Takashi Umemura, Shuji Nakamura, Masashi Yoshida

    The American Journal of Cardiology   90 ( 1 )   5 - 9   2002年7月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/s0002-9149(02)02376-7

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  • Clinical Implication of Persistent Ischemic Chest Pain on Admission in Patients with Late Reperfused Acute Myocardial Infarction.

    Satoshi KURISU, Ichiro INOUE, Takuji KAWAGOE, Masaharu ISHIHARA, Yuji SHIMATANI, Kenji NISHIOKA, Takashi UMEMURA, Suji NAKAMURA, Masashi YOSHIDA

    Internal Medicine   41 ( 11 )   920 - 924   2002年

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Society of Internal Medicine  

    DOI: 10.2169/internalmedicine.41.920

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  • Does Coronary Stenting Affect Microvascular Circulation in Patients With Anterior Acute Myocardial Infarction? Comparison With Balloon Angioplasty.

    Satoshi Kurisu, Ichiro Inoue, Takuji Kawagoe, Masaharu Ishihara, Yuji Shimatani, Kenji Nishioka, Takashi Umemura, Suji Nakamura, Masashi Yoshida

    Circulation Journal   66 ( 10 )   917 - 920   2002年

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Circulation Society  

    DOI: 10.1253/circj.66.917

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MISC

  • Orally Administered Eicosapentaenoic Acid Attenuates Vascular Oxidative Stress and the Development of Angiotensin-II Induced Aortic Aneurysm Formation

    Toru Mivoshi, Kazufumi Nakamura, Tomoko Yonezawa, Daiji Miura, Masashi Yoshida, Hiroshi Morita, Satoshi Akagi, Kunihisa Kohno, Yukihiro Saito, Yoshifumi Ninomiya, Kengo Kusano, Hiroshi Ito

    CIRCULATION   126 ( 21 )   2012年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Web of Science

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共同研究・競争的資金等の研究

  • 特発性肺動脈性肺高血圧症由来肺動脈平滑筋細胞のエネルギー代謝の解明と治療薬の開発

    研究課題/領域番号:20K08424  2020年04月 - 2023年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    赤木 達, 中村 一文, 吉田 賢司, 伊藤 浩

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    特発性肺動脈性肺高血圧症(Idiopathic pulmonary arterial hypertension: IPAH)由来の培養肺動脈平滑筋細胞(pulmonary artery smooth muscle cells:
    PASMC)及び非肺高血圧症由来の培養肺動脈平滑筋細胞を、常酸素チャンバー及び低酸素チャンバーに72時間培養後、RNA、蛋白サンプルを得て、ピルビン酸脱水素酵素(Pyruvate dehydrogenase: PDH)、ピルビン酸脱水素酵素キナーゼ(PDH kinase 1: PDK1)、乳酸脱水素酵素(lactate dehydrogenase: LDH)の発現を調べた。PDH及びPDK1は、常酸素下及び低酸素下いずれにおいてもIPAH由来PASMCで非IPAH由来PASMCより高発現していた。一方LDHは常酸素下のみIPAH由来PASMCで非IPAH由来PASMCより高発現し、細胞内乳酸も常酸素下のみIPAH由来PASMCで多かった。以上からIPAH由来PASMCでは常酸素下で解糖系が亢進していることが明らかとなった。
    次にフラックスアナライザーを用いてIPAH由来PASMC、非IPAH由来PASMCのミトコンドリア代謝を調べた。常酸素、低酸素いずれもミトコンドリア代謝が非IPAH由来PASMCと比べ、IPAH由来PASMCで低下し、解糖系によるエネルギー代謝が亢進していた、ところがATP産生を調べてみると、常酸素下では非IPAH由来PASMCと比べPAH由来PASMCでATP産生が低下していたが、低酸素下では逆にIPAH由来PASMCでのATP産生が非IPAH由来PASMCを上回っていた。この結果からIPAH由来PASMCではミトコンドリア代謝が比較的保たれていることが示唆された。

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  • 大動脈解離におけるインテグリンを介した病態機序の解明と新規治療の基盤構築

    研究課題/領域番号:18K08758  2018年04月 - 2021年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    三好 亨, 中村 一文, 米澤 朋子, 吉田 賢司, 伊藤 浩

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    α1インテグリン欠損マウスを用いて、lysyl oxidase 阻害薬とアンジオテンシンIIの皮下投与による大動脈解離モデルの作成を行った。α1インテグリン欠損マウスにおける大動脈解離の発生率は有意に対照マウスに比べて低率であった。C57/BL6マウスを対照群として、腹部大動脈解離の遺伝子発現について、さらに詳細に検討をおこなったところ、炎症性サイトカイン、細胞外マトリックス分解酵素の発現もα1インテグリン欠損マウスで有意に低値であった。インテグリンα1から下流のシグナルについて、MAPK経路のリン酸化がインテグリンα1に関与していることが明らかとなった。

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  • 特発性肺動脈性肺高血圧症由来心筋細胞の特性解明と新規治療薬の開発

    研究課題/領域番号:17K09498  2017年04月 - 2020年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    赤木 達, 中村 一文, 斎藤 幸弘, 吉田 賢司, 伊藤 浩

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    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

    特発性肺動脈性肺高血圧症は著明な肺動脈の上昇から右室機能低下を来す疾患である。現在の治療薬は肺血管に作用するものだけで、右室に直接作用する薬剤はない。今回我々は特発性肺動脈性肺高血圧症の線維芽細胞からiPS細胞を作成し、心筋細胞への誘導に成功した。この心筋細胞には低酸素下のみならず常酸素下でも解糖系にエネルギー代謝を頼っている特性があることを明らかにした。

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  • 腹部大動脈瘤の形成・進展におけるインテグリンの関与とその治療に向けた基盤構築

    研究課題/領域番号:15K09157  2015年04月 - 2018年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    三好 亨, 中村 一文, 米澤 朋子, 吉田 賢司, 伊藤 浩

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    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    腹部大動脈瘤は発見されてもその進展を完全に抑制することは臨床上困難であり、一旦破裂するとその予後は極めて不良である。本研究では、腹部大動脈瘤の進展にα1インテグリンという細胞接着因子が関与することを、遺伝子改変ネズミを用いた実験で明らかにした。α1インテグリンが欠損すると、腹部大動脈瘤の破裂が有意に抑制された。α1インテグリンを標的とした新しい治療戦略の基盤となる結果が得られた。

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  • 遠隔虚血プレコンディショニングを用いた造影剤腎症への総合的治療法の開発

    研究課題/領域番号:15K09141  2015年04月 - 2018年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    伊藤 浩, 中村 一文, 三好 亨, 吉田 賢司, 丸山 徹

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    配分額:4680000円 ( 直接経費:3600000円 、 間接経費:1080000円 )

    虚血性心疾患の診断・治療においては心臓カテーテル検査が必要となる場合があるが、一部の患者において合併疾患としての腎機能低下により、検査後の造影剤腎症を発症することがある。遠隔虚血プレコンディショニングにその予防効果があることが臨床的に示されているが、本研究ではそのメカニズムを検討した。血液中に循環するエクソソームという粒子の中身が遠隔プレコンディショニングにより変化することが明らかとなり、とくにマイクロRNAの変化が重要であることが明らかとなった。この結果は、造影剤腎症の新たな治療戦略の基盤となる情報を提供すると考えている。

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  • ヒト心臓内幹細胞から心筋細胞への分化制御機構の解明

    研究課題/領域番号:25860603  2013年04月 - 2015年03月

    日本学術振興会  科学研究費助成事業  若手研究(B)

    吉田 賢司

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    配分額:4030000円 ( 直接経費:3100000円 、 間接経費:930000円 )

    心筋分化前後のヒト心臓内幹細胞に対してDNA microarrayで発現遺伝子解析を行った結果、ヒト心臓内幹細胞をラット新生児心筋細胞と共培養をすることで、ヒト内皮細胞にかかわる遺伝子群の発現が亢進していた。ヒト心筋細胞にかかわる遺伝子群に関してはヒト用DNA microarrayのチップにラットの遺伝子が反応したため、結果の解析には注意が必要と考えた。逆にヒト血管内皮細胞とヒト心臓内幹細胞を共培養すると、ヒト心臓内幹細胞が一過性に心筋様細胞に分化することがわかった。今後はヒト心筋細胞にかかわる遺伝子群の注意深い解析とともに、ヒト心臓内幹細胞が内皮細胞に分化する機序を探索する予定である。

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  • KCNH2(HERG)電流活性化因子の同定と作用の検討

    研究課題/領域番号:24591054  2012年04月 - 2015年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    中村 一文, 森田 宏, 吉田 賢司, 伊藤 浩

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    配分額:5070000円 ( 直接経費:3900000円 、 間接経費:1170000円 )

    心不全患者の予後改善のためには、心室性不整脈の機序を解明し、新たな治療ターゲットを探すことが必要である。KCNH2 (HERG) チャネルは、先天性QT延長症候群・先天性QT短縮症候群などの原因チャネルであり、心筋の再分極相において最も感受性の強い分子の一つである。我々は心室性不整脈を有する心不全患者の循環血液中にKCNH2(HERG)電流活性化因子を発見した。またKCNH2(HERG)に結合する抗体をWestern blottingにてみつけている。

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  • 腹部大動脈瘤におけるCD44の分子病態制御機構の解明と新たな治療法の基礎確立

    研究課題/領域番号:24591053  2012年04月 - 2015年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    三好 亨, 中村 一文, 米澤 朋子, 吉田 賢司

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    配分額:4940000円 ( 直接経費:3800000円 、 間接経費:1140000円 )

    ヒト大動脈瘤組織におけるCD44の発現と細胞外マトリックス分解の関連の検討ならびに、腹部動脈瘤モデルを用いたCD44を介する炎症性遺伝子ネットワークの解明を行い、CD44が慢性炎症におけるヒアルロン酸分解産物によるシグナル伝達に重要な分子であることが明らかとなった。それによって、CD44を標的とした分子イメージングならびに薬物送達システム開発への基礎を固めることができた。

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  • 加齢によるヒト心臓内幹細胞の役割変化の包括的解析

    研究課題/領域番号:23790855  2011年 - 2012年

    日本学術振興会  科学研究費助成事業  若手研究(B)

    吉田 賢司

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    配分額:4420000円 ( 直接経費:3400000円 、 間接経費:1020000円 )

    本研究では新生児と幼児ヒト心臓内幹細胞を対象として研究を行い、老化によるヒト心臓内幹細胞の役割変化を明らかにしてヒト心臓内幹細胞の心筋分化効率向上を試みた。幼児心臓内幹細胞は新生児心臓内幹細胞と比べすでに生体内で老化しており、心臓内幹細胞として扱った細胞は「前駆細胞」の性質をしていることが判明した。また新生児心臓内幹細胞は心筋分化を、幼児心臓内幹細胞は血管分化を生じやすくなっており、老化に伴い心筋細胞の再生能が低下していることが分かった。DNAマイクロアレイを用いることでIGF1受容体の発現が低下することにより心筋分化から血管分化を生じやすい性質に変化していることを突き止めた。

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担当授業科目

  • アンチエイジング特論 (2023年度) 特別  - その他

  • アンチエイジング特論(医学) (2023年度) 特別  - その他

  • 循環器内科学(基本臨床実習) (2023年度) 特別  - その他

  • 循環器系(臓器・系別統合講義) (2023年度) 特別  - その他

  • アンチエイジング特論(医学) (2022年度) 特別  - その他

  • 循環器内科学(基本臨床実習) (2022年度) 特別  - その他

  • 循環器系(臓器・系別統合講義) (2022年度) 特別  - その他

  • 循環器内科学(基本臨床実習) (2021年度) 特別  - その他

  • 循環器系(臓器・系別統合講義) (2021年度) 特別  - その他

  • 循環器内科学(基本臨床実習) (2020年度) 特別  - その他

  • 循環器系(臓器・系別統合講義) (2020年度) 特別  - その他

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