Analysis of pathological mechanisms of restrictive cardiomyopathy by using cardiac fibroblasts

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17561
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Osaka University
• Principal Investigator: Ishida Hidekazu 大阪大学, 医学系研究科, 助教 (50467552)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 拘束型心筋症 / 心筋線維芽細胞 / 心筋細胞 / iPS細胞

Outline of Final Research Achievements

We conducted whole exome sequence in pediatric restrictive cardiomyopathy (RCM) patients. We analyzed 26 RCM patients and found pathological variants in 17 of 26 patients. The most major variants were observed in troponin I gene. We established cardiac fibroblasts (CFs) from RCM patients. The CFs from RCM were not significantly altered from healthy CFs in terms of proliferation, migration, attachment, apoptosis, and miofbroblasts. The RCM-CFs were co-cultured with healthy cardiomyocytes. We found that co-cultured cardiomyocytes with RCM-CFs deteriorated the diastolic function. We identified several candidates of humoral and contact factors which might be associated with the impaired diastolic function of cardiomyocytes.

Free Research Field

小児循環器学

Academic Significance and Societal Importance of the Research Achievements

小児期発症の拘束型心筋症患者において、網羅的な遺伝子解析を行い、26例中17例で病原性バリアントを同定した。これはこれまで報告された拘束型心筋症の解析例のうち最多である。また、拘束型心筋症患者から採取した心筋線維芽細胞は、健常な心筋細胞の拡張能を悪化させることを発見し、それに関係する可能性がある因子を同定した。すなわち、拘束型心筋症では、心筋細胞だけでなく心筋線維芽細胞も主体的に病気の発症に関わっており、今後、心筋線維芽細胞をターゲットとする新たな治療法の開発につながる成果をあげることが出来た。