Striated muscle-specific β(1D)-integrin and FAK are involved in cardiac myocyte hypertrophic response pathway

Can G. Pham, Alice E. Harpf, Rebecca S. Keller, Hoa T. Vu, Shaw Yung Shai, Joseph C. Loftus, Robert S. Ross

Research output: Contribution to journalArticle

104 Scopus citations

Abstract

Alterations in the extracellular matrix occur during the cardiac hypertrophic process. Because integrins mediate cell-matrix adhesion and β(1D)-integrin (β1D) is expressed exclusively in cardiac and skeletal muscle, we hypothesized that β1D and focal adhesion kinase (FAK), a proximal integrin-signaling molecule, are involved in cardiac growth. With the use of cultured ventricular myocytes and myocardial tissue, we found the following: 1) β1D protein expression was upregulated perinatally; 2) α1-adrenergic stimulation of cardiac myocytes increased β1D protein levels 350% and altered its cellular distribution; 3) adenovirally mediated overexpression of β1D stimulated cellular reorganization, increased cell size by 250%, and induced molecular markers of the hypertrophic response; and 4) overexpression of free β1D cytoplasmic domains inhibited α1-adrenergic cellular organization and atrial natriuretic factor (ANF) expression. Additionally, FAK was linked to the hypertrophic response as follows: 1) coimmunoprecipitation of β1D and FAK was detected; 2) FAK overexpression induced ANF-luciferase; 3) rapid and sustained phosphorylation of FAK was induced by α1-adrenergic stimulation; and 4) blunting of the α1-adrenergically modulated hypertrophic response was caused by FAK mutants, which alter Grb2 or Src binding, as well as by FAK-related nonkinase, a dominant interfering FAK mutant. We conclude that β1D and FAK are both components of the hypertrophic response pathway of cardiac myocytes.

Original languageEnglish (US)
Pages (from-to)H2916-H2926
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume279
Issue number6 48-6
DOIs
StatePublished - 2000

Keywords

  • Cell signaling
  • Extracellular matrix
  • Focal adhesion kinase
  • Heart
  • Neonatal rat ventricular myocytes

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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