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Prevention of Cardiac Hypertrophy in Mice by Calcineurin Inhibition

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Science  11 Sep 1998:
Vol. 281, Issue 5383, pp. 1690-1693
DOI: 10.1126/science.281.5383.1690

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Abstract

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 β-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.

  • * To whom correspondence should be addressed. E-mail: molkj0{at}chmcc.org

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