Do calcineurin inhibitors (cyclosporin and FK506) prevent cardiac hypertrophy in rodent models of hypertrophic cardiomyopathy and pressure-overload hypertrophy?
Calcineurin inhibition prevents cardiac hypertrophy in rodent models, identifying a critical pathogenic pathway and suggesting a potential therapeutic strategy for human hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy (HCM) is an inherited form of heart disease that affects 1 in 500 individuals. Here it is shown that calcineurin, a calcium-regulated phosphatase, plays a critical role in the pathogenesis of HCM. Administration of the calcineurin inhibitors cyclosporin and FK506 prevented disease in mice that were genetically predisposed to develop HCM as a result of aberrant expression of tropomodulin, myosin light chain-2, or fetal beta-tropomyosin in the heart. Cyclosporin had a similar effect in a rat model of pressure-overload hypertrophy. These results suggest that calcineurin inhibitors merit investigation as potential therapeutics for certain forms of human heart disease.
Sussman et al. (Fri,) studied this question.
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