PREVENTION OF CARDIAC-HYPERTROPHY IN MICE BY CALCINEURIN INHIBITION

Hypertrophic cardiomyopathy (HCM) is an inherited form of heart diseas e that affects 1 in 500 individuals. Here it is shown that calcineurin , a calcium-regulated phosphatase, plays a critical role in the pathog enesis of HCM. Administration of the calcineurin inhibitors cyclospori n and FK506 prevented disease in mice that were genetically predispose d to develop HCM as a result of aberrant expression of tropomodulin, m yosin Light chain-2, or fetal beta-tropomyosin in the heart. Cyclospor in had a similar effect in a rat model of pressure-overload hypertroph y. These results suggest that calcineurin inhibitors merit investigati on as potential therapeutics for certain forms of human heart disease.