The roles of polarization of macrophages in cardiac fibrosis

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K19369
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: The University of Tokyo
• Principal Investigator: Hajime Abe 東京大学, 医学部附属病院, 特任臨床医 (50746576)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 心不全 / 炎症 / マクロファージ / 心臓リモデリング

Outline of Final Research Achievements

While macrophages seem to play a key role in cardiac remodeling, their precise functions still remain unclear. In this study, we investigated the roles of cardiac macrophages in the process of cardiac remodeling using Transverse aortic constriction (TAC) model. Macrophages can be classified into 2 broad phenotypes, namely M1 macrophages and M2 macrophages. Most of the recruited cells at day 3 were M1 macrophages and day 7 were M2 macrophages. We have previously reported that the hypoxia response transcription factor, HIF-1a, plays an essential role in M1 macrophages activation. To verify the roles of M1 macrophages in cardiac remodeling, we subsequently generated macrophage specific HIF-1a knockout mice (mHIF-1a CKO). FACS analysis revealed that M1 macrohpages accumulation was significantly decreased and more prominent cardiac fibrosis in mHIF-1a CKO mice after TAC. These results demonstrate a novel functional link between M1 macrophages and cardiac remodeling.

Free Research Field

細胞分子生物学