The study investigating the effects of non-neuronal cardiac cholinergic system on intervention of the metabolic remodelling

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460333
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Nippon Medical School
• Principal Investigator: Kakinuma Yoshihiko 日本医科大学, 医学(系)研究科(研究院), 教授 (40233944)
• Co-Investigator(Renkei-kenkyūsha): SATO TAKAYUKI 高知大学, 教育研究部医療学系, 教授 (90205930)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: アセチルコリン / 心臓 / 非神経性心臓コリン作動系

Outline of Final Research Achievements

In vivo biological functions of a non-neuronal cardiac cholinergic system (NNCCS) was investigated using the heart-specific ChAT tg mice (ChAT tgm), in which choline acetyltransferase (ChAT) gene was overexpressed under the control of an alpha MHC promoter. ChAT tgm showed comparable hemodynamic parameters and cardiac functions, compared with WT mice. ChAT tgm was resistant against myocardial infarction with a remarkably improved survival rate, more intact myocardium in the infarcted area as well as enhanced angiogenesis, and more glucose uptake in cardiomyocytes, compared with WT mice. Isolated ChAT tgm hearts showed a longer beating period even in the global ischemia and faster recovery of beating after ischemia canceled. These results suggest that NNCCS can be a therapeutic target against cardiovascular diseases.

Free Research Field

循環器内科学