A new paradigm of heart failure with preserved ejection fraction : Elucidation of pathology focusing on vascular smooth mascle cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15907
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Kurume University
• Principal Investigator: Shibata Tatsuhiro 久留米大学, 医学部, 助教 (20776942)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: HFpEF / SOCS3 / JAK/STAT経路

Outline of Final Research Achievements

The purpose of this study is to clarify the possibility that the STAT3 pathway of vascular smooth muscle cells plays an important role in the pathogenesis of heart failure with preserved ejection fraction(HFpEF). Therefore, the applicant used smooth muscle cell specific SOCS3-KO mice to evaluate age-related changes. As a result, echocardiography showed significant diastolic dysfunction in the KO group, macroscopically, cardiac hypertrophy and epicardial thickening, and the cardiac weight/ body weight ratio also increased significantly. Furthermore, in the KO group, epicardial thickening and myocardial fibrosis were significantly caused with aging, STAT3 activation was also significant, and a significant increase in serum IL-6 was also observed. From the above, it is considered that the activation of STAT3 associated with chronic inflammation may be strongly involved.

Free Research Field

分子循環器学

Academic Significance and Societal Importance of the Research Achievements

高齢化社会の進展に伴い、我が国ではHFpEFの占める割合が増加しているが、HFpEFには未だ予後改善をもたらす治療法はまだ確立されていない。そこで、本研究ではHFpEFにおける慢性炎症が心臓・動脈の両者に与える影響を検討し、また平滑筋細胞に焦点をあてて解明することで、病態を統一的に理解し、この理解に基づいてHFpEFの新たな治療開発の基盤となる知見を得ることが期待できる。