NFAT Transcription Factors Are Critical Survival Factors That Inhibit Cardiomyocyte Apoptosis During Phenylephrine Stimulation In Vitro

摘要: Biomechanical stress on the heart results in activation of numerous signaling cascades, leading to cardiomyocyte hypertrophy, apoptosis, and ultimately, failure. The Ca 2+ -dependent phosphatase calcineurin is an essential mediator cardiac most but not all studies, inhibition attenuated hypertrophy vivo. However, has been reported have adverse effects remodeling apoptosis. Calcineurin regulates activity a number downstream targets, including transcription factors NFAT, MEF2, NF-κB, apoptotic factor Bad. To evaluate contribution NFAT by responses hypertrophic stimulation, we used adenovirus express VIVIT, selective peptide inhibitor calcineurin-mediated activation. We found that during phenylephrine stimulation inhibited resulted increased In contrast, nonselective cyclosporin A did cause apoptosis after stimulation. Cyclosporin suppressed effect VIVIT These demonstrate activates both pro- antiapoptotic pathways cardiomyocytes, critical component pathway whether outcome or survival.