| First Author | Wang Y | Year | 2019 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1865 |
| Issue | 6 | Pages | 1170-1181 |
| PubMed ID | 30639224 | Mgi Jnum | J:275797 |
| Mgi Id | MGI:6303731 | Doi | 10.1016/j.bbadis.2019.01.011 |
| Citation | Wang Y, et al. (2019) Deficiency of mouse mast cell protease 4 mitigates cardiac dysfunctions in mice after myocardium infarction. Biochim Biophys Acta Mol Basis Dis 1865(6):1170-1181 |
| abstractText | Mouse mast cell protease-4 (mMCP4) is a chymase that has been implicated in cardiovascular diseases, including myocardial infarction (MI). This study tested a direct role of mMCP4 in mouse post-MI cardiac dysfunction and myocardial remodeling. Immunoblot and immunofluorescent double staining demonstrated mMCP4 expression in cardiomyocytes from the infarct zone from mouse heart at 28day post-MI. At this time point, mMCP4-deficient Mcpt4(-/-) mice showed no difference in survival from wild-type (WT) control mice, yet demonstrated smaller infarct size, improved cardiac functions, reduced macrophage content but increased T-cell accumulation in the infarct region compared with those of WT littermates. mMCP4-deficiency also reduced cardiomyocyte apoptosis and expression of TGF-beta1, p-Smad2, and p-Smad3 in the infarct region, but did not affect collagen deposition or alpha-smooth muscle actin expression in the same area. Gelatin gel zymography and immunoblot analysis revealed reduced activities of matrix metalloproteinases and expression of cysteinyl cathepsins in the myocardium, macrophages, and T cells from Mcpt4(-/-) mice. Immunoblot analysis also found reduced p-Smad2 and p-Smad3 in the myocardium from Mcpt4(-/-) mice, yet fibroblasts from Mcpt4(-/-) mice showed comparable levels of p-Smad2 and p-Smad3 to those of WT fibroblasts. Flow cytometry, immunoblot analysis, and immunofluorescent staining demonstrated that mMCP4-deficiency reduced the expression of proapoptotic cathepsins in cardiomyocytes and protected cardiomyocytes from H2O2-induced apoptosis. This study established a role of mMCP4 in mouse post-MI dysfunction by regulating myocardial protease expression and cardiomyocyte death without significant impact on myocardial fibrosis or survival post-MI in mice. |
