Comprehensive Searching for Circulating mircoRNAs as a Novel Biomarker for Pulmonary Arterial Hypertension

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09474
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Nagasaki University
• Principal Investigator: EGUCHI Masamichi 長崎大学, 病院(医学系), 助教 (70585405)
• Co-Investigator(Kenkyū-buntansha): 池田 聡司 長崎大学, 医歯薬学総合研究科(医学系), 講師 (10336159) ; 前村 浩二 長崎大学, 医歯薬学総合研究科(医学系), 教授 (90282649)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 肺動脈性肺高血圧症 / バイオマーカ / micro RNA

Outline of Final Research Achievements

Pulmonary arterial hypertension(PAH) is a frequent complication in connective tissue diseases (CTD) and is associated with a high degree of mortality. Micro RNAs(miRNAs) function in various cellular activities. However, the role of miRNA in connective tissue disease-pulmonary arterial hypertension (CTD-PAH) is not fully understood. We assessed the hypothesis that whether serum miRNA expression can serve as a novel biomarker of CTD-PAH and evaluates the possibility that miRNA is involved in the pathogenesis of CTD-PAH. The expression miR-4674 was increased in the patients with CTD-PAH. High miR-4674 expression correlated with mean PA pressure. Next, we investigated the gain and loss of miR-4674 function by analyzing the bioactivity of pulmonary arterial smooth muscle cells (hPASMC). miRNA-4674 increased cells proliferation and protect cells against apoptosis. Interference with this pathway may offer novel approaches to treating CTD-PAH.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

肺動脈性肺高血圧症(PAH)は、昨今、新しい治療薬が開発されてはいるが、いまだ予後不良の疾患である。特に膠原病性肺動脈性肺高血圧症(CTD-PAH)の予後は非常に悪い。本研究結果はCTD-PAHの早期発見が可能となり、予後の改善が可能となる、また、既存の治療薬とは異なる、新しいPAHの治療ターゲットとなり得る事が示唆され、CTD-PAHの患者の予後をさらに改善することが期待できる。