Prevention of cardiac hypertrophy in mice by calcineurin inhibition

Mark A. Sussman, Hae W. Lim, Natalie Gude, Tyler Taigen, Eric N. Olson, Jeffrey Robbins, Melissa C. Colbert, Antonio Gualberto, David F. Wieczorek, Jeffery D. Molkentin

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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 β-tropomyosin in the heart. Cyclosporin had a similar effect in a rat model or pressure-overload hypertrophy. These results suggest that calcineurin inhibitors.

Original languageEnglish (US)
Pages (from-to)1690-1693
Number of pages4
JournalScience
Volume281
Issue number5383
DOIs
Publication statusPublished - Sep 11 1998

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Sussman, M. A., Lim, H. W., Gude, N., Taigen, T., Olson, E. N., Robbins, J., ... Molkentin, J. D. (1998). Prevention of cardiac hypertrophy in mice by calcineurin inhibition. Science, 281(5383), 1690-1693. https://doi.org/10.1126/science.281.5383.1690