tropisetron and Diabetic-Cardiomyopathies

Cardiomyocyte hypertrophy is an important structural feature of diabetic cardiomyopathy. Calcineurin/nuclear factor of activated T-cell (NFAT) pathway plays a central role in the pathogenesis of cardiac hypertrophy. The purpose of this study was to investigate the effects of tropisetron, a novel calcineurin inhibitor, on high glucose (HG)-induced cardiomyocyte hypertrophy and its underlying mechanism.. H9c2 myocardial cells were treated with tropisetron or cyclosporine A 1 h before exposure to HG for 48 h.. Exposure to HG resulted in enhanced cell size, protein content and atrial natriuretic peptide (ANP) protein expression. HG significantly increased Ca(2+) level, calcineurin expression and nuclear translocation of NFATc4. Both tropisetron and cyclosporine A markedly prevented the hypertrophic characteristic features, calcineurin overexpression and nuclear localization of NFATc4 while intracellular Ca(2+) was not affected.. Our results showed that tropisetron may have protective effects against HG-induced cardiomyocyte hypertrophy. The mechanism responsible for this beneficial effect seems to be, at least in part, blockade of calcineurin/NFAT signalling pathway.

Topics: Active Transport, Cell Nucleus; Animals; Atrial Natriuretic Factor; Calcineurin; Calcineurin Inhibitors; Calcium; Cardiomegaly; Cell Line; Cell Size; Cytoprotection; Diabetic Cardiomyopathies; Glucose; Indoles; Myocytes, Cardiac; Nerve Tissue Proteins; NFATC Transcription Factors; Rats; Signal Transduction; Tropisetron