Title : Tumor necrosis factor induces matrix metalloproteinases in cardiomyocytes and cardiofibroblasts differentially via superoxide production in a PI3Kgamma-dependent manner.

Pub. Date : 2010 Mar

PMID : 20007453






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1 Tumor necrosis factor induces matrix metalloproteinases in cardiomyocytes and cardiofibroblasts differentially via superoxide production in a PI3Kgamma-dependent manner. Superoxides tumor necrosis factor Mus musculus
2 In response to recombinant TNF (rTNF, 20 ng/ml), cardiomyocytes exhibited faster and more pronounced superoxide production compared with cardiofibroblasts, concomitant with increased expression of several MMPs. Superoxides tumor necrosis factor Mus musculus
3 We identified phosphatidylinositol 3-kinase (PI3K)gamma as a key factor in TNF-mediated events since TNF-induced superoxide production, MMP expression, and activity were significantly suppressed in cardiomyocytes and cardiofibroblasts deficient in PI3Kgamma. Superoxides tumor necrosis factor Mus musculus
4 We identified phosphatidylinositol 3-kinase (PI3K)gamma as a key factor in TNF-mediated events since TNF-induced superoxide production, MMP expression, and activity were significantly suppressed in cardiomyocytes and cardiofibroblasts deficient in PI3Kgamma. Superoxides tumor necrosis factor Mus musculus
5 We further demonstrated that the TNF-superoxide-MMP axis of events is in fact activated in heart disease in vivo. Superoxides tumor necrosis factor Mus musculus
6 Our study demonstrates that TNF triggers expression and activation of MMPs faster and stronger in cardiomyocytes than in cardiofibroblasts in a superoxide-dependent manner and via activation of PI3Kgamma, thereby contributing to adverse myocardial remodeling in disease. Superoxides tumor necrosis factor Mus musculus