Protein Kinase Cα Negatively Regulates Systolic and Diastolic Function in Pathological Hypertrophy

Harvey S. Hahn, Yehia Marreez, Amy Odley, Amber Sterbling, Martin G. Yussman, K. Chad Hilty, Ilona Bodi, Stephen B. Liggett, Arnold Schwartz, Gerald W. Dorn

Research output: Contribution to journalArticle

99 Scopus citations

Abstract

The protein kinase C (PKC) family is implicated in cardiac hypertrophy, contractile failure, and β-adrenergic receptor (βAR) dysfunction. Herein, we describe the effects of gain- and loss-of-PKCα function using transgenic expression of conventional PKC isoform translocation modifiers. In contrast to previously studied PKC isoforms, activation of PKCα failed to induce cardiac hypertrophy, but instead caused βAR insensitivity and ventricular dysfunction. PKCα inhibition had opposite effects. Because PKCα is upregulated in human and experimental cardiac hypertrophy and failure, its effects were also assessed in the context of the Gαq overexpression model (in which PKCα is transcriptionally upregulated). Normalization (inhibition) of PKCα activity in Gαq hearts improved systolic and diastolic function, whereas further activation of PKCα caused a lethal restrictive cardiomyopathy with marked interstitial fibrosis. These results define pathological roles for PKCα as a negative regulator of ventricular systolic and diastolic function.

Original languageEnglish
Pages (from-to)1111-1119
Number of pages9
JournalCirculation research
Volume93
Issue number11
DOIs
StatePublished - Nov 28 2003
Externally publishedYes

Keywords

  • Interstitial fibrosis
  • Protein kinase C
  • Restrictive cardiomyopathy
  • Systolic and diastolic heart failure

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    Hahn, H. S., Marreez, Y., Odley, A., Sterbling, A., Yussman, M. G., Hilty, K. C., Bodi, I., Liggett, S. B., Schwartz, A., & Dorn, G. W. (2003). Protein Kinase Cα Negatively Regulates Systolic and Diastolic Function in Pathological Hypertrophy. Circulation research, 93(11), 1111-1119. https://doi.org/10.1161/01.RES.0000105087.79373.17