The association between miR27a and ischemic cardiomyopathy.

2019 Fiscal Year Final Research Report

• Project/Area Number: 19K21296
• Project/Area Number (Other): 18H06191 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Yamagata University
• Principal Investigator: Narumi Taro 山形大学, 医学部, 客員研究員 (00755142)
• Project Period (FY): 2018-08-24 – 2020-03-31
• Keywords: microRNA / 線維化 / 心筋 / 肥大 / 機序

Outline of Final Research Achievements

Hypertension causes cardiac remodeling, including hypertrophy and interstitial fibrosis, which leads to development of hypertensive heart disease (HHD). Although microRNA-21 (miR-21) is associated with fibrogenesis in multiple organs, its impact on hypertrophic cardiac remodeling in hypertension is not known. Circulating miR-21 level was higher in patients with HHD than that in the control subjects. It also positively correlated with serum myocardial fibrotic markers. In vitro, mirVana-miR-21-specific inhibitor attenuated Ang II-induced PDCD4 downregulation and contributed to subsequent deactivation of AP-1/TGF-β1 signaling pathway in neonatal rat cardiomyocytes. Thus,　suppression of miR-21 prevents hypertrophic cardiac remodeling by regulating PDCD4, AP-1, and TGF-β1 signaling pathway.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

TGF-β1はmiR-21の発現を上昇させるとともに、miR-21も下流の標的遺伝子を介してTGF-β1を上昇させる。フィードバックループが形成され心筋リモデリングを促進する。HHD患者においてmiR-21が上昇しており、左室肥大や心筋の線維化の形成には、miR-21/PDCD4/TGF-β1の経路が重要な役割を果たしていると考えられた。miR-21を阻害することでAng IIによるTGF-β1増加を抑制することができた。miR-21阻害薬は心筋細胞のTGF-β1シグナル抑制を介して心筋リモデリングを抑制できる可能性が示唆された。miR-21は左室肥大リモデリングの治療標的になる可能性がある。