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 language | English (US) |
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Pages (from-to) | H2916-H2926 |
Journal | American Journal of Physiology - Heart and Circulatory Physiology |
Volume | 279 |
Issue number | 6 48-6 |
DOIs | |
State | Published - 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)