Monoclonal hematopoiesis in heart failure

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08523
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Fukushima Medical University
• Principal Investigator: Takeishi Yasuchika 福島県立医科大学, 医学部, 教授 (40272067)
• Co-Investigator(Kenkyū-buntansha): 三阪 智史 福島県立医科大学, 医学部, 助教 (50793080) ; 横川 哲朗 福島県立医科大学, 医学部, 助教 (80748773) ; 池田 和彦 福島県立医科大学, 医学部, 教授 (90381392)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: clonal hematopoiesis / JAK2V617F / pulmonary hypertension / ACVRL1 / ALK1

Outline of Final Research Achievements

Clonal hematopoiesis is a risk factor for cardiovascular diseases. We identified JAK2V617F-positive clonal hematopoiesis in patients with pulmonary hypertension. JAK2V617F exacerbated hypoxia-induced pulmonary hypertension and pulmonary arterial remodeling in mice. JAK2V617F progressively upregulated Acvrl1 (encoding ALK1) during the differentiation from bone marrow stem/progenitor cells into mature lung neutrophils, and the ALK1 inhibition blocked the development of pulmonary hypertension. Clonal hematopoiesis with JAK2V617F may be a novel therapeutic target for pulmonary hypertension.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

加齢に伴って造血幹細胞に突然変異が生じると、単一クローンに由来する血液細胞の増殖が末梢血中に観察される。これは加齢と心血管疾患を結ぶ現象として注目される。ALK1阻害薬がJAK2変異クローン性造血を有する肺高血圧症に有効な治療戦略となる可能性がある。