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• W2092103544 abstract "Oxidative stress causes cardiomyocyte death and subsequent ventricular dysfunction and cardiac remodeling after myocardial infarction (MI), thus contributing to high mortality in chronic heart failure patients. We investigated the effects of kallistatin in cardiac remodeling in a chronic MI rat model and in primary cardiac cells. Human kallistatin gene was injected intramyocardially 20 min after ligation of the left coronary artery. At 4 weeks after MI, expression of human kallistatin in rat hearts was identified by reverse transcription–polymerase chain reaction, immunohistochemistry and ELISA. Kallistatin administration improved cardiac performance, increased mean arterial pressure, decreased myocardial infarct size and restored left ventricular wall thickness. Kallistatin treatment significantly attenuated cardiomyocyte size and atrial natriuretic peptide expression. Kallistatin also reduced collagen accumulation, collagen fraction volume and expression of collagen types I and III, transforming growth factor-β1 (TGF-β1) and plasminogen activator inhibitor-1 in the myocardium. Inhibition of cardiac hypertrophy and fibrosis by kallistatin was associated with increased cardiac nitric oxide (NO) levels and decreased superoxide formation, NADH oxidase activity and p22-phox expression. Moreover, in both primary cultured rat cardiomyocytes and myofibroblasts, recombinant kallistatin inhibited intracellular superoxide formation induced by H2O2, and the antioxidant effect of kallistatin was abolished by Nω-nitro-L-arginine methyl ester (L-NAME), indicating a NO-mediated event. Kallistatin promoted survival of cardiomyocytes subjected to H2O2 treatment, and inhibited H2O2-induced Akt and ERK phosphorylation, as well as NF-κB activation. Furthermore, kallistatin abrogated TGF-β-induced collagen synthesis and secretion in cultured myofibroblasts. This is the first study to demonstrate that kallistatin improves cardiac performance and prevents post-MI-induced cardiac hypertrophy and fibrosis through its antioxidant action." @default.
• W2092103544 created "2016-06-24" @default.
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• W2092103544 date "2008-11-01" @default.
• W2092103544 modified "2023-09-27" @default.
• W2092103544 title "Role of kallistatin in prevention of cardiac remodeling after chronic myocardial infarction" @default.
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• W2092103544 doi "https://doi.org/10.1038/labinvest.2008.85" @default.
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