Transgenic overexpression of constitutively active protein kinase C epsilon causes concentric cardiac hypertrophy

Circ Res. 2000 Jun 23;86(12):1218-23. doi: 10.1161/01.res.86.12.1218.


To test the hypothesis that activation of the protein kinase C (PKC) epsilon isoform leads to cardiac hypertrophy without failure, we studied transgenic mice with cardiac-specific overexpression of a constitutively active mutant of the PKCepsilon isoform driven by an alpha-myosin heavy chain promoter. In transgenic mice, the protein level of PKCepsilon in heart tissue was increased 9-fold. There was a 6-fold increase of the membrane/cytosol ratio, and PKC activity in the membrane fraction was 4.2-fold compared with wild-type mice. The heart weight was increased by 28%, and upregulation of the mRNA for beta-myosin heavy chain and alpha-skeletal actin was observed in transgenic mouse hearts. Echocardiography demonstrated increased anterior and posterior wall thickness with normal left ventricular function and dimensions, indicating concentric cardiac hypertrophy. Isolated cardiomyocyte mechanical function was slightly decreased, and Ca(2+) signals were markedly depressed in transgenic mice, suggesting that myofilament sensitivity to Ca(2+) was increased. No differences were observed in either the levels of cardiac Ca(2+)-handling proteins or the degree of cardiac regulatory protein phosphorylation between wild-type and transgenic mice. Unlike mice with PKCbeta(2) overexpression, transgenic mice with cardiac-specific overexpression of the active PKCepsilon mutant demonstrated concentric hypertrophy with normal in vivo cardiac function. Thus, PKC isoforms may play differential functional roles in cardiac hypertrophy and failure.

Publication types

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

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cardiomegaly / diagnostic imaging
  • Cardiomegaly / etiology*
  • Cardiomegaly / genetics
  • Cardiomegaly / pathology
  • Cell Separation
  • Echocardiography
  • Gene Expression
  • Heart / physiopathology
  • Homeostasis
  • Isoenzymes / metabolism*
  • Lung / physiology
  • Mice
  • Mice, Transgenic / genetics
  • Mice, Transgenic / physiology
  • Muscle Proteins / metabolism
  • Muscle Proteins / physiology
  • Myocardium / metabolism
  • Myocardium / pathology
  • Organ Size
  • Phosphorylation
  • Protein Kinase C / metabolism*
  • Protein Kinase C-epsilon


  • Isoenzymes
  • Muscle Proteins
  • Prkce protein, mouse
  • Protein Kinase C
  • Protein Kinase C-epsilon
  • Calcium