Prevention of cardiac hypertrophy in mice by calcineurin inhibition.
basic_science · Level V
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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 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.
Medical subject headings
- Calcineurin Inhibitors
- Cardiac Myosins
- Cardiomegaly
- Cardiomyopathy, Dilated
- Cardiomyopathy, Hypertrophic
- Cyclosporine
- Microfilament Proteins
- Myocardium
- Tacrolimus