National Cerebral and Cardiovascular

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Research Institute

Department of Cardiac Physiology

 

Member

DirectorJames T. Pearson
Laboratory ChiefHirotsugu Tsuchimochi
Kenji Mori
Senior ResearcherKentaro Hirose
Mark T. Waddingham
Postdoctoral FellowMd. Junayed Nayeem

 

Research

Our basic research aims to understand the common and unique mechanisms of metabolic dysregulation that drive cardiopulmonary and renal dysfunction over the life course in settings of hypertension, obesity, insulin resistance, premature ageing and various cardiomyopathies (including inherited forms).
We use gold standard echocardiography and pressure-volumetry to assess cardiac function and the biomechanical properties of the ventricles during the early development of dysfunction and the progression to heart failure. Moreover, we utilize our unique synchrotron radiation based in vivo muscle diffraction technique and fast, high resolution microangiography to investigate the complex interactions between the microcirculation and the in situ cardiomyocyte contraction-relaxation mechanisms. Similarly, microangiography and laser Doppler flowmetry are used to probe the mechanisms of vascular dysfunction in the renal, pulmonary and cerebral circulations. More recently, we also perform investigations of isolated primary cardiomyocytes from our many disease models.
Increasingly, we are incorporating techniques to integrate the molecular basis of these disease states with physiological function, including western blotting, real time PCR, SYPRO-ProQ staining and other techniques to determine the contributions of an altered transcriptome and posttranslational protein modifications. Our research greatly benefits from international collaborations with the Universities of Otago, Bochum, Copenhagen, Wurzburg, Heidelberg and Monash University.

Selected Publications

  1. Sonobe T, H Tsuchimochi, H Maeda, JT Pearson. Increased contribution of KCa channels to muscle contraction induced vascular and blood flow responses in sedentary and exercise trained ZFDM rats. J Physiol 2022 Jun, 600(12):2919-2938. doi: 10.1113/JP282981.
  2. Waddingham MT, Tsuchimochi H, Sonobe T, Asano R, Jin H, Ow CPC, Schwenke DO, Katare R, Aoyama K, Umetani K, Hoshino M, Uesugi K, Shirai M, Ogo T, Pearson JT. Using synchrotron radiation imaging techniques to elucidate the actions of hexarelin in the heart of small animal models. Front Physiol. 2022 Jan, 12:766818. doi:10.3389/fphys.2021.766818.
  3. Pearson JT, Thambyah HP, Waddingham MT, Inagaki T, Sukumaran V, Ngo JP, Ow CPC, Sonobe T, Chen YC, Edgley AJ, Fujii Y, Du C-K, Zhan D-Y, Umetani K, Kelly DJ, Tsuchimochi H, Shirai M. Beta-blockade prevents coronary macro and microvascular dysfunction induced by a high salt diet and insulin resistance in the Goto-Kakizaki rat. Clinical Sci. 2021 Jan 135(2):327-346. doi: 10.1042/CS20201441.
  4. Sonobe T, Akiyama T, Pearson JT. Carrier-mediated serotonin efflux induced by pharmacological anoxia in the rat heart in vivo. Clin Exp Pharmacol Physiol. 2021 Dec, 48:1685-1692. doi:10.1111/1440-1681.13576.
  5. Inocencio I, Tran NT, Nakamura S, Khor SJ, Wiersma M, Stoecker K, Maksimenko A, Polglase GR, Walker DW, Pearson JT, Wong FY. Cerebral haemodynamic response to somatosensory stimulation in preterm and 7-10-day old term lambs: direct synchrotron microangiography assessment. J Cerebral Blood Flow Metab. 2021 Sep, 271678X211045848. doi:10.1177/0271678X211045848.
  6. Rabaglino MB, M. Wakabayashi, JT Pearson, LL Jensen. Effect of age on the vascular proteome in middle cerebral arteries and mesenteric resistance arteries in mice. Mechanisms of Ageing and Development 2021 Dec, 200;111594. doi: 10.1016/j.mad.2021.111594.
  7. Lew JK, Pearson JT, Saw E, Tsuchimochi H, Wei M, Ghosh N, Du CK, Zhan DY, Jin M, Umetani K, Shirai M, Katare R, Schwenke DO. Exercise regulates microRNAs to preserve coronary and cardiac function in the diabetic heart. Circ Res. 2020 Nov, 127(11):1384-1499. doi: 10.1161/CIRCRESAHA.120.317604.
  8. Sukumaran V, H Tsuchimochi, T Sonobe, MT Waddingham, M Shirai, JT Pearson. Liraglutide treatment improves the coronary microcirculation in insulin resistant Zucker obese rats on a high salt diet. Cardiovasc Diabetol. 2020 Feb, 19:24. doi: 10.1186/s12933-020-01000-z.
  9. Waddingham MT, T Sonobe, H Tsuchimochi, AJ Edgley, V Sukumaran, Y-C Chen, SS Hansra, DO Schwenke, K Umetani, K Aoyama, N Yagi, DJ Kelly, S Gaderi, M Herwig, D Kolijn, A Mügge, WJ Paulus, T Ogo, M Shirai, N Hamdani, JT Pearson. Diastolic dysfunction is initiated by cardiomyocyte impairment ahead of endothelial dysfunction due to increased oxidative stress and inflammation in an experimental prediabetes model. J Mole Cell Cardiol. 2019 Dec, 137:119-131. doi: 10.1016/j.yjmcc.2019.10.005.
  10. Sukumaran V, H Tsuchimochi, T Sonobe, M Shirai, JT Pearson. Liraglutide improves renal endothelial function in obese Zucker rats on a high salt diet. J Pharmacol Exp Ther 2019 Jun, 369(3):375-388. doi: 10.1124/jpet.118.254821.

last updated : 2023/04/03

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