Reversal of cardiac hypertrophy in transgenic disease models by calcineurin inhibition

J Mol Cell Cardiol. 2000 Apr;32(4):697-709. doi: 10.1006/jmcc.2000.1113.


Heart disease remains one of the leading causes of morbidity and mortality in the industrialized nations of the world. Intense investigation has centered around identifying and manipulating intracellular signaling pathways that direct hypertrophic and myopathic responses in an attempt to intervene in the progression or reverse certain forms of heart disease. We show here that cyclosporin A-mediated inhibition of the calcium-regulated phosphatase, calcineurin (PP2B), reverses cardiac hypertrophy and myopathic dilation in two transgenic mouse models of cardiomyopathy. Reversal was demonstrated by gravimetric analysis, echocardiography, histological analysis, and molecular analysis of hypertrophy-associated gene expression. In contrast, a third mouse model of hypertrophic cardiomyopathy due to activated NFAT3 cardiac-specific expression was not affected by cyclosporin A. These results suggest that calcineurin may function in the long-term maintenance of cardiac hypertrophy or myopathic disease states.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcineurin / genetics
  • Calcineurin Inhibitors*
  • Cardiomegaly / physiopathology*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cyclosporine / pharmacology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Disease Models, Animal
  • Enzyme Inhibitors / pharmacology*
  • Mice
  • Mice, Transgenic
  • Microfilament Proteins*
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Phenotype
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Tropomodulin


  • Calcineurin Inhibitors
  • Carrier Proteins
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Microfilament Proteins
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Tmod1 protein, mouse
  • Transcription Factors
  • Tropomodulin
  • Cyclosporine
  • Calcineurin