期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 53, 期 5, 页码 599-608出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2012.07.017
关键词
Myocardial infarction; Matrix metalloproteinase-9; Extracellular matrix; Inflammation; Cardiac remodeling; Macrophage
资金
- T32 [HL07446]
- American Heart Association [09POST2150178]
- NSF [0649172]
- NIH [EB009496, 1SC2 HL101430]
- NHLBI HHSN [268201000036C (N01-HV-00244)]
- Max and Minnie Tomerlin Voelcker Fund [R01 HL075360]
- Veteran's Administration (Merit)
- [HL075360S1]
- Div Of Engineering Education and Centers
- Directorate For Engineering [0649172] Funding Source: National Science Foundation
Following myocardial infarction (MI), activated macrophages infiltrate into the necrotic myocardium as part of a robust pro-inflammatory response and secrete matrix metalloproteinase-9 (MMP-9). Macrophage activation, in turn, modulates the fibrotic response, in part by stimulating fibroblast extracellular matrix (ECM) synthesis. We hypothesized that overexpression of human MMP-9 in mouse macrophages would amplify the inflammatory and fibrotic responses to exacerbate left ventricular dysfunction. Unexpectedly, at day 5 post-MI, ejection fraction was improved in transgenic (TG) mice (25 +/- 2%) compared to the wild type (WT) mice (18 +/- 2%; p<0.05). By gene expression profiling, 23 of 84 inflammatory genes were decreased in the left ventricle infarct (LVI) region from the TG compared to WT mice (all p < 0.05). Concomitantly, TG macrophages isolated from the LVI, as well as TG peritoneal macrophages stimulated with LPS, showed decreased inflammatory marker expression compared to WT macrophages. In agreement with attenuated inflammation, only 7 of 84 cell adhesion and ECM genes were increased in the TG LVI compared to WT LVI, while 43 genes were decreased (all p<0.05). These results reveal a novel role for macrophage-derived MMP-9 in blunting the inflammatory response and limiting ECM synthesis to improve left ventricular function post-MI. (C) 2012 Elsevier Ltd. All rights reserved.
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