2017 Fiscal Year Final Research Report

Synchrotron radiation investigation of cardiac contractile protein dynamics at end diastole in a type 2 prediabetes model rat

Research Project

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Project/Area Number	16K15452
Research Category	Grant-in-Aid for Challenging Exploratory Research
Allocation Type	Multi-year Fund
Research Field	Cardiovascular medicine
Research Institution	National Cardiovascular Center Research Institute
Principal Investigator	SHIRAI Mikiyasu 国立研究開発法人国立循環器病研究センター, 研究所, 特任研究員 (70162758)
Co-Investigator(Kenkyū-buntansha)	土持裕胤国立研究開発法人国立循環器病研究センター, 研究所, 室長 (60379948) Pearson James 国立研究開発法人国立循環器病研究センター, 研究所, 部長 (30261390)
Co-Investigator(Renkei-kenkyūsha)	TO Seikon 国立研究開発法人国立循環器病研究センター, 研究所, 上級研究員 (90590646) KIN Mika 国立研究開発法人国立循環器病研究センター, 研究所, 研究員 (40746773) SEN Toun 国立研究開発法人国立循環器病研究センター, 研究所, 派遣研究員 (30616941) INAGAKI Tadakatsu 国立研究開発法人国立循環器病研究センター, 研究所, 上級研究員 (20638366)
Research Collaborator	YAGI Naoto
Project Period (FY)	2016-04-01 – 2018-03-31
Keywords	循環器・高血圧 / 糖尿病 / 心臓拡張機能障害 / 心筋収縮タンパク質 / 放射光X線回折法
Outline of Final Research Achievements	Applying our synchrotron radiation X-ray diffraction approach to the beating heart of the type 2 prediabetes Goto-Kakizaki (GK) rat, we found abnormal cardiac contractile protein dynamics in the subendocardium was associated with left ventricular diastolic dysfunction. GK rat hearts did not show altered phosphorylation state of the small myofilament proteins, but showed hypophosphorylation of titin. Myocardial soluble guanylate cyclase (sGC) protein expression and PKG activity were significantly depressed, and hypophosphorylation of titin correlated with depressed sGC-PKG activation. Synchrotron radiation microangiography enabled us to visualize the coronary circulation, which suggested that the GK rat does not have coronary endothelial dysfunction at this age, and therefore the previously hypothesised role of depressed endothelium dependent nitric oxide signaling driving diastolic dysfunction is not supported.
Free Research Field	循環生理学