Protease Activated Receptor-2 Contributes to Heart Failure

Heart failure is a major clinical problem worldwide. Previous studies have demonstrated an important role or G protein coupled receptors, including protease-activated receptors (PARs), in the pathology of heart hypertrophy and failure Activation of PAR-2 on cardiomyacytes has been shown to induce hypertrophic growth in vitro. PAR-2 also contributes to myocardial infarction and heart remodeling after ischenliaireperfusion injury. In this study, we found that PAR-2 induced hypertrophic growth of cultured rat neonatal carcliomyocytes in a MEK1/2 and p38 dependent manner. In addition, PAR-2 activation on mouse cardiornyocytes increased expression of the pro-fibrotic chernakme MCP-1. Furthermore, cardiomyocyte-specific overexpression of PAR-2 in mice induced heart hypertrophy, cardiac fibrosis, inflammation and heart failure. Finally, in a mouse model of myocardial infarction induced by permanent ligation of the left anterior descending coronary artery, PAR-2 deficiency attenuated heart remodeling and improved heart function independently of its contribution to the size of the initial infarct. Taken together, our data indicate that PAR-2 signaling contributes to pathogenesis of hypertrophy and heart failure.