Old and new tools to dissect calcineurin's role in pressure-overload cardiac hypertrophy.

摘要: In the last several years, a number of experiments have implicated pivotal role calcium/calmodulin-calcineurin dependent pathway as final common signaling mechanism by which diverse hypertrophic stimuli converge to mediate responses in cardiomyocytes. Calcineurin inhibitors, i.e. cyclosporine A (CsA) and FK506, can interrupt pathway, thereby preventing cardiac hypertrophy. The data that convincingly support this novel hypothesis were derived either from vitro studies cultured cardiomyocytes or vivo transgenic mice. However, when was tested clinically relevant animal models hypertrophy, controversial results conclusions emerged. conventional two questions remain be answered: (1) whether calcineurin is activated hypertrophied muscle, (2) inhibitors prevent addition, clinical observations revealed appear exert pro-hypertrophic effects organ transplant recipients. controversies suggest current are blunt tools for testing pressure-overload hypertrophy vivo, because there so many confounding associated with systemic administration drugs. As such, new genetic approaches may overcome some problems pharmacological inhibitors. This invited review will focus on surrounding ability inhibition (pressure-overload) address question.