Regulation of cardiac remodeling by inhibiting the PGD2-mediated inflammatory response.

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15199
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: The University of Tokyo
• Principal Investigator: Ikeda Yuichi 東京大学, 医学部附属病院, 特任准教授 (10744419)
• Co-Investigator(Kenkyū-buntansha): 熊谷 英敏 東京大学, 医学部附属病院, 特任助教 (20281008) ; 森田 啓行 東京大学, 医学部附属病院, 講師 (60323573) ; 篠原 正和 神戸大学, 医学(系)研究科(研究院), 研究員 (80437483)
• Co-Investigator(Renkei-kenkyūsha): URADE Yoshihiro 筑波大学, 国際統合睡眠医科学研究機構, 教授 (10201360)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 自己免疫性心筋炎 / 心筋線維化 / プロスタグランディンD2 / H-PGDS阻害薬

Outline of Final Research Achievements

Inflammatory response to the cardiomyocyte injury accelerates cardiac remodeling, the pathological process which often determines the clinical course of heart failure. Utilizing the experimental autoimmune myocarditis in mice as a model system, we found that PGD2 produced by H-PGDS contributed to the pathogenesis of cardiac remodeling initiated by local inflammation. In this model, cardiac PGD2 levels were elevated, and the systemic administration of H-PGDS inhibitor decreased the levels of PGD2, resulting in less fibrotic changes in the heart. These findings suggest that inhibition of the local production of PGD2 in the heart is beneficial for suppressing cardiac remodeling. To test if we could generalize our present findings, we established another mouse model based on the mdx mice. Using our second model, we are currently planning to determine if other bioactive lipid mediators produced in the heart are also involved in the pathogenesis of cardiac remodeling.

Free Research Field

薬理学、炎症、免疫、プロスタグランディン