Prevention of Cardiac Hypertrophy in Mice by Calcineurin Inhibition

TLDR

Hypertrophic cardiomyopathy is an inherited heart disease affecting about 1 in 500 individuals. Inhibiting calcineurin with cyclosporin or FK506 prevented hypertrophy in genetically predisposed mice and reduced pressure‑overload hypertrophy in rats, indicating therapeutic promise.

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.