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Extracellular Matrix And Fibroblast Communication Following Myocardial Infarction, Yonggang Ma, Ganesh V. Halade, Merry L. Lindsey
Extracellular Matrix And Fibroblast Communication Following Myocardial Infarction, Yonggang Ma, Ganesh V. Halade, Merry L. Lindsey
Internal Medicine Faculty Publications
The extracellular matrix (ECM) provides structural support by serving as a scaffold for cells, and as such the ECM maintains normal tissue homeostasis and mediates the repair response following injury. In response to myocardial infarction (MI), ECM expression is generally upregulated in the left ventricle (LV), which regulates LV remodeling by modulating scar formation. The ECM directly affects scar formation by regulating growth factor release and cell adhesion and indirectly affects scar formation by regulating the inflammatory, angiogenic, and fibroblast responses. This review summarizes the current literature on ECM expression patterns and fibroblast mechanisms in the myocardium, focusing on the …
Transgenic Overexpression Of Matrix Metalloproteinase-9 In Macrophages Attenuates The Inflammatory Response And Improves Left Ventricular Function Post-Myocardial Infarction, Rogelio Zamilpa, Jessica Ibarra, Lisandra E. De Castro Brás, Trevi A. Ramirez, Nguyen Nguyen, Ganesh V. Halade, Jianhua Zhang, Qiuxia Dai, Tariq Dayah, Ying Ann Chiao, Wesley Lowell, Seema S. Ahuja, Jeanine D'Armiento, Yu Fang Jin, Merry L. Lindsey
Transgenic Overexpression Of Matrix Metalloproteinase-9 In Macrophages Attenuates The Inflammatory Response And Improves Left Ventricular Function Post-Myocardial Infarction, Rogelio Zamilpa, Jessica Ibarra, Lisandra E. De Castro Brás, Trevi A. Ramirez, Nguyen Nguyen, Ganesh V. Halade, Jianhua Zhang, Qiuxia Dai, Tariq Dayah, Ying Ann Chiao, Wesley Lowell, Seema S. Ahuja, Jeanine D'Armiento, Yu Fang Jin, Merry L. Lindsey
Internal Medicine Faculty Publications
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.