Faculty Profiles - WATANABE Shogo

Dietary Salt Restriction Improves Cardiac and Adipose Tissue Pathology Independently of Obesity in a Rat Model of Metabolic Syndrome Reviewed

Takuya Hattori, Tamayo Murase, Miwa Takatsu, Kai Nagasawa, Natsumi Matsuura, Shogo Watanabe, Toyoaki Murohara, Kohzo Nagata

JOURNAL OF THE AMERICAN HEART ASSOCIATION 3 ( 6 ) 2014.12

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Background-Metabolic syndrome (MetS) enhances salt sensitivity of blood pressure and is an important risk factor for cardiovascular disease. The effects of dietary salt restriction on cardiac pathology associated with metabolic syndrome remain unclear.
Methods and Results-We investigated whether dietary salt restriction might ameliorate cardiac injury in DahlS. Z-Leprfa/Leprfa (DS/ obese) rats, which are derived from a cross between Dahl salt-sensitive and Zucker rats and represent a model of metabolic syndrome. DS/obese rats were fed a normal-salt (0.36% NaCl in chow) or low-salt (0.0466% NaCl in chow) diet from 9 weeks of age and were compared with similarly treated homozygous lean littermates (DahlS. Z-Lepr+/Lepr+, or DS/lean rats). DS/ obese rats fed the normal-salt diet progressively developed hypertension and showed left ventricular hypertrophy, fibrosis, and diastolic dysfunction at 15 weeks. Dietary salt restriction attenuated all of these changes in DS/obese rats. The levels of cardiac oxidative stress and inflammation and the expression of cardiac renin-angiotensin-aldosterone system genes were increased in DS/obese rats fed the normal-salt diet, and dietary salt restriction downregulated these parameters in both DS/obese and DS/lean rats. In addition, dietary salt restriction attenuated the increase in visceral adipose tissue inflammation and the decrease in insulin signaling apparent in DS/ obese rats without reducing body weight or visceral adipocyte size. Dietary salt restriction did not alter fasting serum glucose levels but it markedly decreased the fasting serum insulin concentration in DS/obese rats.
Conclusions-Dietary salt restriction not only prevents hypertension and cardiac injury but also ameliorates insulin resistance, without reducing obesity, in this model of metabolic syndrome.

DOI： 10.1161/JAHA.114.001312

Elevated C-Reactive Protein Levels and Enhanced High Frequency Vasomotion in Patients with Ischemic Heart Disease during Brachial Flow-Mediated Dilation Reviewed

Shogo Watanabe, Eisuke Amiya, Masafumi Watanabe, Munenori Takata, Atsuko Ozeki, Aya Watanabe, Shuichi Kawarasaki, Tomoko Nakao, Yumiko Hosoya, Kohzo Nagata, Ryozo Nagai, Issei Komuro

PLOS ONE 9 ( 10 ) 2014.10

Language：English Publishing type：Research paper (scientific journal) Publisher：PUBLIC LIBRARY SCIENCE

Purpose: The physiological role of vasomotion, rhythmic oscillations in vascular tone or diameter, and its underlying mechanisms are unknown. We investigated the characteristics of brachial artery vasomotion in patients with ischemic heart disease (IHD).
Methods: We performed a retrospective study of 37 patients with IHD. Endothelial function was assessed using flow-mediated dilation (FMD), and power spectral analysis of brachial artery diameter oscillations during FMD was performed. Frequency-domain components were calculated by integrating the power spectrums in three frequency bands (in ms(2)) using the MemCalc (GMS, Tokyo, Japan): very-low frequency (VLF), 0.003-0.04 Hz; low frequency (LF), 0.04-0.15 Hz; and high frequency (HF), 0.15-0.4 Hz. Total spectral power (TP) was calculated as the sum of all frequency bands, and each spectral component was normalized against TP.
Results: Data revealed that HF/TP closely correlated with FMD (r = -0.33, p = 0.04), whereas VLF/TP and LF/TP did not. We also explored the relationship between elevated C-reactive protein (CRP) levels and vasomotion. HF/TP was significantly increased in subjects with high CRP levels (CRP;>0.08 mg/dL) compared with subjects with low CRP levels (0.052 +/- 0.026 versus 0.035 +/- 0.022, p<0.05). The HF/TP value closely correlated with CRP (r = 0.24, p = 0.04), whereas the value of FMD did not (r = 0.023, p = 0.84). In addition, elevated CRP levels significantly increased the value of HF/TP after adjustment for FMD and blood pressure (beta = 0.33, p<0.05).
Conclusion: The HF component of brachial artery diameter oscillation during FMD measurement correlated well with FMD and increased in the presence of elevated CRP levels in subjects with IHD.

DOI： 10.1371/journal.pone.0110013

Effect of add-on aliskiren to type 1 angiotensin receptor blocker therapy on endothelial function and autonomic nervous system in hypertensive patients with ischemic heart disease. Reviewed International journal

Atsuko Ozeki, Eisuke Amiya, Masafumi Watanabe, Yumiko Hosoya, Munenori Takata, Aya Watanabe, Shuichi Kawarasaki, Tomoko Nakao, Shogo Watanabe, Kazuko Omori, Namie Yamada, Yukiko Tahara, Yasunobu Hirata, Ryozo Nagai

Journal of clinical hypertension (Greenwich, Conn.) 16 ( 8 ) 591 - 598 2014.8

Language：English Publishing type：Research paper (scientific journal)

The aim of this study was to evaluate the add-on effect of aliskiren to valsartan on endothelial-dependent vasodilation in hypertensive patients with ischemic heart disease (IHD). After 4 weeks of treatment with 80 mg of valsartan, 28 patients were allocated to either continued treatment with valsartan or an add-on treatment with valsartan plus 150 mg of aliskiren. Aliskiren significantly decreased plasma renin activity, whereas endothelium-dependent vasodilation measured by flow-mediated dilation (FMD) did not change. In contrast, heart rate significantly decreased (73.1 ± 9.8 to 66.3 ± 7.0 beats per minute at baseline and 24 weeks, respectively [P = .009]) and the standard deviation of the R-R intervals (SDNN) significantly increased in the aliskiren group. The add-on aliskiren to valsartan therapy may not improve endothelial functions, although it significantly reduced resting heart rate via regulation of the autonomic nervous system in hypertensive patients with IHD.

DOI： 10.1111/jch.12366

Generation of Rat-Induced Pluripotent Stem Cells from a New Model of Metabolic Syndrome Reviewed

Nana Takenaka-Ninagawa, Yuka Kawabata, Shogo Watanabe, Kohzo Nagata, Shigeko Torihashi

PLOS ONE 9 ( 8 ) 2014.8

Language：English Publishing type：Research paper (scientific journal) Publisher：PUBLIC LIBRARY SCIENCE

We recently characterized DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, derived from a cross between Dahl salt-sensitive rats and Zucker rats, as a new animal model of metabolic syndrome (MetS). Although the phenotype of DS/obese rats is similar to that of humans with MetS, the pathophysiological and metabolic characteristics in each cell type remain to be clarified. Hence, the establishment of induced pluripotent stem cells (iPSCs) derived from MetS rats is essential for investigations of MetS in vitro. Reports of rat iPSCs (riPSCs), however, are few because of the difficulty of comparing to other rodents such as mouse. Recently, the advantage of using mesenchymal stromal cells (MSCs) as a cell source for generating iPSCs was described. We aimed to establish riPSCs from MSCs in adipose tissues of both DS/obese rats and their lean littermates, DahlS.Z-Lepr(+)/Lepr(+) (DS/lean) rats using lentivirus vectors with only three factors Oct4, Klf4, and Sox2 without c-Myc. The morphology, gene expression profiles, and protein expression of established colonies showed embryonic stem cell (ESCs)like properties, and the differentiation potential into cells from all three germ layers both in vitro and in vivo (teratomas). Both riPSCs became adipocytes after induction of adipogenesis by insulin, T3, and dexamethasone. Real-time PCR analysis also revealed that both riPSCs and the adipose tissue from DS/obese and DS/lean rats possess similar expression patterns of adipocyte differentiation-related genes. We succeeded in generating riPSCs effectively from MSCs of both DS/obese and DS/ lean rats. These riPSCs may well serve as highly effective tools for the investigation of MetS pathophysiology in vitro.

DOI： 10.1371/journal.pone.0104462

Diurnal body temperature rise is reduced in diabetes with autonomic neuropathy. Reviewed International journal

Eisuke Amiya, Masafumi Watanabe, Munenori Takata, Tomoko Nakao, Yumiko Hosoya, Shogo Watanabe, Ryozo Nagai, Issei Komuro

Clinical autonomic research : official journal of the Clinical Autonomic Research Society 24 ( 2 ) 95 - 7 2014.4

Language：English Publishing type：Research paper (scientific journal)

We conducted a retrospective study of 60 patients with ischemic heart disease (31 with diabetes and 29 without diabetes) to investigate the impact of diabetes on diurnal body temperature patterns. We found that the increase of axillary body temperature in the evening was reduced in the presence of diabetes, which was associated with autonomic neuropathy.

DOI： 10.1007/s10286-013-0223-9

PREMATURE CARDIAC SENESCENCE IN DahlS.Z-Lepr(fa)/Lepr(fa) RATS AS A NEW ANIMAL MODEL OF METABOLIC SYNDROME Reviewed

Keiji Takahashi, Miwa Takatsu, Takuya Hattori, Tamayo Murase, Sae Ohura, Yuuri Takeshita, Shogo Watanabe, Toyoaki Murohara, Kohzo Nagata

NAGOYA JOURNAL OF MEDICAL SCIENCE 76 ( 1-2 ) 35 - 49 2014.2

Language：English Publishing type：Research paper (scientific journal) Publisher：NAGOYA UNIV, SCH MED

Aging is accelerated by metabolic and cardiovascular diseases, and the risk of these diseases increases with age. Obesity is an important risk factor for many age-related diseases and is linked to reduced telomere length in white blood cells. We investigated whether cardiac senescence might be enhanced in DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, which we recently established as a new animal model of metabolic syndrome. The heart of DS/obese rats was compared with that of homozygous lean littermates (DahlS.Z-Lepr(+)/Lepr(+), or DS/lean, rats). DS/obese rats manifested hypertension as well as left ventricular hypertrophy, fibrosis, and diastolic dysfunction at 18 weeks of age. Myocardial oxidative stress and inflammation were increased in DS/obese rats compared with DS/lean rats. Telomere length in myocardial cells did not differ between the two rat strains, whereas telomerase activity and expression of the telomerase reverse transcriptase gene were increased in DS/obese rats. Expression of the senescence-associated genes for checkpoint kinase 2 (Chk2), p53, and p21 as well as that of genes related to the renin-angiotensin-aldosterone system were also up-regulated in the DS/obese rat heart. Our results indicate that DS/obese rats undergo premature cardiac senescence as well as cardiac remodeling in association with the development of diastolic dysfunction in these animals.

GLUCOCORTICOIDS ACTIVATE CARDIAC MINERALOCORTICOID RECEPTORS IN ADRENALECTOMIZED DAHL SALT-SENSITIVE RATS Reviewed

Masafumi Ohtake, Takuya Hattori, Tamayo Murase, Keiji Takahashi, Miwa Takatsu, Mayuko Ohtake, Masaaki Miyachi, Shogo Watanabe, Xian Wu Cheng, Toyoaki Murohara, Kohzo Nagata

NAGOYA JOURNAL OF MEDICAL SCIENCE 76 ( 1-2 ) 59 - 72 2014.2

Language：English Publishing type：Research paper (scientific journal) Publisher：NAGOYA UNIV, SCH MED

We previously showed that selective mineralocorticoid receptor (MR) blockade by eplerenone is cardioprotective in Dahl salt-sensitive (DS) rats. To clarify the consequences of glucocorticoid-mediated MR activation in these animals, we investigated the effects of exogenous corticosterone on blood pressure as well as cardiac remodeling and function after adrenalectomy. DS rats were subjected to adrenalectomy at 6 weeks of age and thereafter fed a high-salt diet and administered corticosterone (20 mg/kg per day) or vehicle. Systolic blood pressure was higher in the corticosterone group than in the vehicle group at 7 weeks and thereafter. By 11 weeks, corticosterone had reduced left ventricular (LV) mass and induced LV diastolic dysfunction. The ratio of collagen type I to type III mRNA levels in the left ventricle was increased in the corticosterone group compared with the vehicle group. Administration of a non-antihypertensive dose of the MR antagonist spironolactone (20 mg/kg per day) from 6 weeks inhibited the effects of corticosterone on both the collagen type I to type III mRNA ratio and diastolic function without affecting the decrease in LV mass. Spironolactone attenuated both the increase in NADPH oxidase activity in the left ventricle and coronary vascular inflammatory responses apparent in the corticosterone group. These results indicate that exogenous glucocorticoids induce hypertension, cardiac remodeling, and diastolic dysfunction in adrenalectomized DS rats fed a high-salt diet. The cardiac effects of exogenous glucocorticoids are likely attributable, at least in part, to myocardial oxidative stress and coronary vascular inflammation induced by glucocorticoid-activated MRs..

Differences in Body Temperature Variability Between Subjects With and Without Diabetes and Predictive Value for Cardiovascular Events Reviewed

Eisuke Amiya, Masafumi Watanabe, Munenori Takata, Shogo Watanabe, Atsuko Ozeki, Aya Watanabe, Shuichi Kawarasaki, Tomoko Nakao, Yumiko Hosoya, Kazuko Omori, Koji Maemura, Yasunobu Hirata, Ryozo Nagai, Issei Komuro

CIRCULATION JOURNAL 77 ( 7 ) 1844 - 1853 2013.7

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPANESE CIRCULATION SOC

Background: Differences in regulating factors and the clinical implications of body temperature variability (BTV) between subjects with and without diabetes have not been clarified to date.
Methods and Results: In 66 subjects with ischemic heart disease (33 with diabetes and 33 without diabetes), BTV, the difference between the highest and lowest temperature measurements, and body temperature standard deviation (BT SD) were measured from axillary body temperature (ABT) records of 3 consecutive days and followed for 16.4 +/- 8.4 months. In subjects without diabetes BTV and BT SD were closely associated with endothelial function as evaluated on flow-mediated dilation (BTV, R=0.33, P=0.026; BT SD, R=0.41, P=0.029), whereas there was a poor association in subjects with diabetes. In the absence of an interrelationship between vascular function and thermoregulation, the contribution of inflammation to BTV was increased in subjects with diabetes (BTV, 0.59 +/- 0.21 degrees C for C-reactive protein [CRP] <0.08 mg/dl vs. 0.79 +/- 0.28 degrees C for CRP >0.08 mg/dl, P=0.014). Event-free survival analysis showed that in subjects with diabetes higher BT SD was associated with shorter event-free survival (log-rank P=0.012), but this relationship was not found in subjects without diabetes.
Conclusions: In subjects with diabetes, the interrelationship between thermoregulation and vascular function was disrupted and the effect of inflammation on thermoregulation was enhanced, so that BTV had a sufficient predictive value for cardiovascular events in diabetic subjects.

DOI： 10.1253/circj.CJ-12-1591

Simultaneous heart rate variability monitoring enhances the predictive value of flow-mediated dilation in ischemic heart disease Reviewed

Shogo Watanabe, Eisuke Amiya, Masafumi Watanabe, Munenori Takata, Atsuko Ozeki, Aya Watanabe, Shuichi Kawarasaki, Tomoko Nakao, Yumiko Hosoya, Kazuko Omori, Koji Maemura, Issei Komuro, Ryozo Nagai

Circulation Journal 77 ( 4 ) 1018 - 1025 2013

Language：English Publishing type：Research paper (scientific journal)

Background: Endothelial dysfunction and autonomic nervous system imbalance are both risk markers of atherosclerotic vascular damage. The relationship between these 2 factors, however, has not been clarified concisely. Methods and Results: Flow-mediated dilation (FMD) was measured in 47 patients with ischemic heart disease (IHD
mean age, 68.1±7.1 years) using an ultrasound semi-automatic measuring system (UNEXEF18G), and autonomic nervous system activity was evaluated by simultaneous measurements of heart rate variability. FMD was significantly correlated with standard deviation of normal-to-normal beats (r=0.33, P=0.022) and the power ratio of low-frequency power to high-frequency power (LF/HF
r=-0.38, P=0.0087). Furthermore, multiple regression analysis indicated that LF/HF was the most important predictor of the magnitude of FMD. This interaction was severely blunted by β-blockers and the presence of diabetes. Moreover, standardized FMD according to autonomic nervous system activity was a better predictor of future cardiovascular events than FMD. Subjects with cardiovascular events had a significantly smaller corrected FMD (event (+), 3.62±0.41
event (-), 5.10±2.35
P=0.001), and the higher corrected FMD was associated with longer event-free survival. Conclusions: Autonomic nervous system activity is an important regulatory factor of FMD in subjects with IHD. Assessment of this interaction can help provide more accurate risk stratification of subjects with IHD.

DOI： 10.1253/circj.CJ-12-1043

Scopus

New Mathematical Model of Isometric Twitch Force-response Curve by Skeletal Muscle Contraction ; Using Extended Hybrid Logistic Model Reviewed

The relationship between Fusion index ? Frequency Curve of Displacement ? MMG and Fiber Composition of Skeletal Muscle Reviewed

渡辺彰吾, 北脇知己, 岡久雄

バイオメカニズム 20 2017 - 216 2011

Mathemaical equation of fusion index of tetanic contraction of skeletal muscles Reviewed

Shogo WATANABE, Tomoki KITAWAKI, Hisao OKA

Journal of electromyography and kinesiology 2010

変位筋音図のFusion index曲線と筋線維構成比との関係 Reviewed

渡辺彰吾, 北脇知己, 岡久雄

バイオメカニズム２０ 20 207 - 216 2010

KITAWAKI Tomoki, WATANABE Shogo, OKA Hisao

Transactions of Japanese Society for Medical and Biological Engineering 47 ( 2 ) 199 - 208 2009

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Japanese Society for Medical and Biological Engineering

Isometric force response curve by electrically stimulated skeletal muscle contraction of twitch is important in order to judge the ability of the skeletal muscle and to distinguish disease state. In this report, we introduce a new mathematical model of the isometric force response curve, in order to estimate the muscle contraction behavior accurately. The new mathematical model of force response curve was expressed by a difference of fundamental function which was expressed by products of a step response function and a logistic function. The mathematical model was applied to the force response curve by electrically stimulated muscle contraction of twitch, using the rat gastrocnemius muscle (GC), intermediate vastus muscle (VI) and soleus muscle (SOL) . The results indicate new mathematical model showed better agreement with the force response curve of twitch than previous mathematical model in the rat skeletal muscle which has different muscle fiber type only changes the model parameters.

DOI： 10.11239/jsmbe.47.199

CiNii Article

CiNii Books

Other Link： http://search.jamas.or.jp/link/ui/2009345502

Estimation of skeletal muscle fatigue by a displacement MMG : in the case of isometric elbow flexion at 80% MVC Reviewed

石井圭, 渡辺彰吾, 岡久雄

電子情報通信学会技術研究報告(MEとバイオサイバネティックス 108 ( 479 ) 2009

Consideration of Tetanic Contraction Properties of Different Skeletal Muscle Fibers Using Displacement MMG Reviewed

WATANABE Shogo, KURIYAMA Yuki, KITAWAKI Tomoki, OKA Hisao

Biomechanisms 19 23 - 33 2008

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Society of Biomechanisms

<p>Mechanomyogram (MMG) which measures the slight vibration of muscle contraction can evaluate the mechanical function of the muscle. There are few reports describing the surface displacement (displacement-MMGs) along the cross-section direction during tetanus. Using the laser displacement sensor, we recorded the displacement-MMGs of the human Rectus Femoris (type Ⅱ superiority) and Abductor Pollicis Brevis (type I superiority) during tetanus with a 30-s continuous electrostimulation at the frequency ranging from 0.2 to 50 [Hz], and discussed the contraction properties of these mixed fiber-type skeletal muscles. Three male and one female subjects (21- to 25-year-old) without medical histories of muscular disease joined the experiment repeatedly. The results showed that incomplete tetanus in the mixed fiber-type skeletal muscles were induced by two steps, and the displacement-MMG amplitude was affected by the component ratio of the area of muscle fiber. Furthermore, according to contraction and relaxation time of muscle force in type I, II twitches, the frequency regions of the first phase of incomplete tetanus and the second almost corresponded with those of type I and type II, respectively.</p>

DOI： 10.3951/biomechanisms.19.23

CiNii Article

Development of displacement MMG sensor using a photo-reflector Reviewed

岡久雄, 栗山雄樹, 渡辺彰吾, 北脇知己, 岡本基

電子情報通信学会技術研究報告(MEとサイバネティックス) 107 ( 541 ) 2008

Evaluation of muscle fatigue with the different muscle fiber type during running exercise using MMG Reviewed

栗山雄樹, 渡辺彰吾, 北脇知己, 岡久雄

電子情報通信学会技術研究報告(MEとサイバネティックス) 106 ( 592 ) 2007

Consideration of Running Form Using Lower Leg Electrical Impedance Reviewed

中村隆夫, 北脇知己, 渡辺彰吾, 楠原俊昌, 矢野博己, 池田敏, 加藤浩, 山本尚武, 岡久雄

電子情報通信学会技術研究報告 107 ( 154 ) 2007

Muscle contraction accelerates IL-6 mRNA expression in the rat masseter muscle. Reviewed International journal

Tsuyoshi Ono, Kenji Maekawa, Shogo Watanabe, Hisao Oka, Takuo Kuboki

Archives of oral biology 52 ( 5 ) 479 - 86 2007

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: This study was conducted to determine if interleukin-6 (IL-6) and interleukin-1beta (IL-1beta) mRNA expression increase in response to muscle contraction caused by repetitive electrical stimulation of the rat masseter muscle. METHODS: Male Wistar rats weighing 140-160 g were divided randomly into the following three groups: electrical stimulation (ES) group (n=21), carrageenan injection (CI) group (n=24), and ES under dantrolene sodium (muscle relaxant) injection (ESDI) group (n=7). ES or CI was done to the left masseter; and mock ES or mock CI to the right. Muscle tissues on both sides were sampled for total RNA isolation. Real-time RT-PCR was performed, with the cyclophilin A (CypA) mRNA level in each sample as an internal control. Mean relative IL-6 (il-6/cypA) and IL-1beta (il-1beta/cypA) mRNA levels were compared between the experimental and mock-treated sides within each group. RESULTS: Mean IL-6/CypA levels in the ES- or CI-treated muscle significantly increased, without any significant incremental change observed in either mock-treated muscle. Interestingly, the increase in the il-6/cypA level caused by the ES was suppressed by the injection of dantrolene sodium in the ESDI group. Furthermore, the mean il-1beta/cypA level in the CI-treated masseter also significantly increased without any significant incremental change observed in the mock-treated muscle. However, there was no significant difference in the mean il-1beta/cypA levels in the masseter between the ES- and the mock-treated sides. CONCLUSIONS: These results show that IL-6 mRNA expression in the rat masseter muscle was accelerated by the CI or by repetitive muscle contraction induced by ES. Since the mRNA level of IL-1beta, a well-known proinflammatory cytokine, was not altered by the contraction, the accelerated IL-6 mRNA expression elicited by the muscle contraction does not seem to be related to local inflammation.

DOI： 10.1016/j.archoralbio.2006.10.025