Calcineurin plays a critical role in the development of pressure overload-induced cardiac hypertrophy

Background-Although activation of the Ca2+-dependent phosphatase calcineuri n has been reported to induce cardiomyocyte hypertrophy, whether calcineuri n is involved in pressure overload-induced cardiac hypertrophy remains cont roversial. Methods and Results-We examined in the present study the role of calcineuri n in pressure overload-induced cardiac hypertrophy using transgenic mice th at overexpress the dominant negative mutant of calcineurin specifically in the heart. There were no significant differences in body weight, blood pres sure, heart rate, heart weight, and the cardiac calcineurin activity betwee n the transgenic mice and their littermate wild-type mice at basal state. T he activity of calcineurin was markedly increased by pressure overload prod uced by constriction of the abdominal aorta in the heart of wild-type mice but less increased in the heart of the transgenic mice. Pressure overload i nduced increases in heart weight, wall thickness of the left ventricle, and diameter of cardiomyocytes; reprogramming of expressions of immediate earl y response genes and fetal-type genes; activation of extracellular signal-r egulated protein kinases; and fibrosis. All these hypertrophic responses we re more prominent in the wild-type mice than in the transgenic mice. Conclusions-These results suggest that calcineurin plays a critical role in the development of pressure overload-induced cardiac hypertrophy.