Prevention of cardiac hypertrophy in mice by calcineurin inhibition

MA Sussman, HW Lim, N Gude, T Taigen, EN Olson… - Science, 1998 - science.org
MA Sussman, HW Lim, N Gude, T Taigen, EN Olson, J Robbins, MC Colbert, A Gualberto…
Science, 1998science.org
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 …
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.
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