Development of strategy for treatment of cardiavc failure based on the nderstanding of pathogenesis and gene abnormalities

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293181
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Kimura Akinori 東京医科歯科大学, 難治疾患研究所, 教授 (60161551)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 遺伝子 / 遺伝学 / ゲノム / 循環器・高血圧 / 生体分子

Outline of Final Research Achievements

In this study, identification of gene abnormalities in hereditary cardiomyopathy and their pathogenesis were invesigated. It was revealed that the increased calcium sensitivity could directly cause hypertrophic cardiomyopathy in a mouse model and its pathogenesis was inhibited by a ROCK2 inhibirtor. In addition, molecular mechanisms for gender differences in dilated cardiomyopathy caused by lamin A/C gene mutations was found to involve transport of androgen receptor with FHL2 resulting in SRF-mediated expression of genes for cardiac remodeling. Moreover, several novel disease genes for hereditary cardiomyopathy were identified by a linkage study in a large multiplex family with hypertrophic cardiomyaopathy and by candidate gene approaches for hypertrophic cardiomyopathy and dilated cardiomyopathy. Functional abnormalities caused by the mutations in these novel disease genes were also investigated to reveal the molecular pathogenesis of cardiomyopathies.

Free Research Field

人類遺伝学