Role of phospholipase A2 receptor in cardiovascular disease and drug development

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07041
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: University of Yamanashi
• Principal Investigator: Kugiyama Kiyotaka 山梨大学, 大学院総合研究部, 教授 (00225129)
• Co-Investigator(Kenkyū-buntansha): 中村 和人 山梨大学, 大学院総合研究部, 助教 (30456488) ; 渡辺 一広 山梨大学, 大学院総合研究部, 臨床助教 (50535549)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 炎症 / 心血管病

Outline of Final Research Achievements

In this study, we elucidated the role and mechanism of action of secretory phospholipase A2 (sPLA2) and its receptor, PLA2 receptor, in the onset and pathophysiology of cardiovascular disease. That is, we found that Group V sPLA2 is involved in aortic dissection / rupture and endocytosis of acetyl LDL in macrophages. Furthermore, it was clarified that the sPLA2 receptor is involved in the development of autoimmune myocarditis, and that the soluble type sPLA2 receptor suppresses collagen-I-stimulated cell migration. We have developed a unique ELISA kit for measuring the blood concentration of human soluble type PLA2 receptor. Using this kit, it was revealed that soluble PLA2 receptor blood concentration is an independent biomarker of heart failure.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

PLA2受容体を標的とする薬剤は線維化・リモデリングを制御することでこれらの疾患の治療薬となることが期待される。さらに可溶型PLA2受容体血中濃度が心血管病の新たなバイオマーカーとなることが期待される。炎症後の急性期線維化による組織修復と慢性期の線維化による臓器リモデリングは、心血管病のみならず他臓器疾患にも広く関与しており、本研究によって得られる知見を他臓器疾患にも応用できる。