Journal article

Diastolic dysfunction is initiated by cardiomyocyte impairment ahead of endothelial dysfunction due to increased oxidative stress and inflammation in an experimental prediabetes model

Mark T Waddingham, Takashi Sonobe, Hirotsugu Tsuchimochi, Amanda J Edgley, Vijayakumar Sukumaran, Yi Ching Chen, Sarabjit S Hansra, Daryl O Schwenke, Keiji Umetani, Kohki Aoyama, Naoto Yagi, Darren J Kelly, Shahrooz Gaderih, Melissa Herwig, Detmar Kolijn, Andreas Muegge, Walter J Paulus, Takeshi Ogo, Mikiyasu Shirai, Nazha Hamdani Show all



Coronary microvessel endothelial dysfunction and nitric oxide (NO) depletion contribute to elevated passive tension of cardiomyocytes, diastolic dysfunction and predispose the heart to heart failure with preserved ejection fraction. We examined if diastolic dysfunction at the level of the cardiomyocytes precedes coronary endothelial dysfunction in prediabetes. Further, we determined if myofilaments other than titin contribute to impairment. Utilizing synchrotron microangiography we found young prediabetic male rats showed preserved dilator responses to acetylcholine in microvessels. Utilizing synchrotron X-ray diffraction we show that cardiac relaxation and cross-bridge dynamics are impaired..

View full abstract


Awarded by National Cerebral and Cardiovascular Center

Awarded by AMED

Awarded by International Synchrotron Access Programme

Awarded by German Research Foundation

Funding Acknowledgements

Intramural Research Funds (11-1-2, 27-2-1) for Cardiovascular Diseases from the National Cerebral and Cardiovascular Center to M.S., N.Y. and J.T.P and AMED 18072597 to J.T.P, H.T. and T.S. Travel support was provided to M.T.W., Y.C.C., S.S.H. and J.T.P. by the International Synchrotron Access Programme (AS/IA111, AS/IA133 and AS/IA143) managed by the Australian Synchrotron and funded by the Australian Government. M.T.W was a recipient of an Australian Postgraduate Award Scholarship from the University of Melbourne. N.H. was supported by German Research Foundation (DFG 5712/2-1).