Transgenic Overexpression of Constitutively Active Protein Kinase C ε Causes Concentric Cardiac Hypertrophy
- 23 June 2000
- journal article
- other
- Published by Wolters Kluwer Health in Circulation Research
- Vol. 86 (12) , 1218-1223
- https://doi.org/10.1161/01.res.86.12.1218
Abstract
—To test the hypothesis that activation of the protein kinase C (PKC) ε isoform leads to cardiac hypertrophy without failure, we studied transgenic mice with cardiac-specific overexpression of a constitutively active mutant of the PKCε isoform driven by an α–myosin heavy chain promoter. In transgenic mice, the protein level of PKCε 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 β-myosin heavy chain and α-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 Ca2+ signals were markedly depressed in transgenic mice, suggesting that myofilament sensitivit...Keywords
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