期刊
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
卷 62, 期 20, 页码 1890-1901出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacc.2013.07.057
关键词
inflammation; macrophage; mesenchymal stroma cell; myocardial infarction; remodeling
资金
- Legacy Heritage Fund of New York
- Israel Ministry of Science, Culture, and Sport
- Seventh Framework Program, European Commission-Cardiovascular Disease
- US-Israel Bi-national Science Foundation
- Israeli National Nanotechnology Initiative and Helmsley Charitable Trust for a focal technology area on nanomedicines for personalized theranostics
Objectives This study sought to investigate the hypothesis that the favorable effects of mesenchymal stromal cells (MSCs) on infarct repair are mediated by macrophages. Background The favorable effects of MSC therapy in myocardial infarction (MI) are complex and not fully understood. Methods We induced MI in mice and allocated them to bone marrow MSCs, mononuclear cells, or saline injection into the infarct, with and without early (4 h before MI) and late (3 days after MI) macrophage depletion. We then analyzed macrophage phenotype in the infarcted heart by flow cytometry and macrophage secretome in vitro. Left ventricular remodeling and global and regional function were assessed by echocardiography and speckle-tracking based strain imaging. Results The MSC therapy significantly increased the percentage of reparative M2 macrophages (F4/80(+)CD206(+)) in the infarcted myocardium, compared with mononuclear-and saline-treated hearts, 3 and 4 days after MI. Macrophage cytokine secretion, relevant to infarct healing and repair, was significantly increased after MSC therapy, or incubation with MSCs or MSC supernatant. Significantly, with and without MSC therapy, transient macrophage depletion increased mortality 30 days after MI. Furthermore, early macrophage depletion produced the greatest negative effect on infarct size and left ventricular remodeling and function, as well as a significant incidence of left ventricular thrombus formation. These deleterious effects were attenuated with macrophage restoration and MSC therapy. Conclusions Some of the protective effects of MSCs on infarct repair are mediated by macrophages, which are essential for early healing and repair. Thus, targeting macrophages could be a novel strategy to improve infarct healing and repair. (C) 2013 by the American College of Cardiology Foundation
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据