β Integrins participate in the hypertrophic response of rat ventricular myocytes

Robert S. Ross, Can Pham, Shaw Yung Shai, Joshua I. Goldhaber, Csilla Fenczik, Chris C. Glembotski, Mark H. Ginsberg, Joseph C. Loftus

Research output: Contribution to journalArticle

151 Scopus citations

Abstract

Multiple signaling pathways have been implicated in the hypertrophic response of ventricular myocytes, yet the importance of cell-matrix interactions has not been extensively examined. Integrins are cell-surface molecules that link the extracellular matrix to the cellular cytoskeleton. They can function as cell signaling molecules and transducers of mechanical information in noncardiac cells. Given these properties and their abundance in cardiac cells, we evaluated the hypothesis that β1 integrin function is involved in the α1-adrenergic mediated hyperophic response of neonatal rat ventricular myocytes. The hypertrophic response of this model required interaction with extracellular matrix proteins. Specificity of these results was confirmed by demonstrating that ventricular myocytes plated onto an anti- β1 integrin antibody supported the hypertrophic gene response. Adenovirus- mediated overexpression of β1 integrin augmented the myocyte hypertrophic response when assessed by protein synthesis and atrial natriuretic factor production, a marker gene of hypertrophic induction. DNA synthesis was not altered by integrin overexpression. Transfection of cultured cardiac myocytes with either the ubiquitously expressed β(1A) integrin or the cardiac/skeletal muscle-specific β1 isoform (β1(D)) activated reporter expression from both the atrial natriuretic factor and myosin light chain-2 ventricular promoters, genetic markers of ventricular cell hypertrophy. Finally, suppression of integrin signaling by overexpression of free β1 integrin cytoplasmic domains inhibited the adrenergically mediated atrial natriuretic factor response. These findings show that integrin ligation and signaling are involved in the cardiac hypertrophic response pathway.

Original languageEnglish (US)
Pages (from-to)1160-1172
Number of pages13
JournalCirculation research
Volume82
Issue number11
DOIs
StatePublished - Jun 15 1998

Keywords

  • Extracellular matrix
  • Hypertrophy
  • Integrin
  • Myocardium
  • Myocyte

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Ross, R. S., Pham, C., Shai, S. Y., Goldhaber, J. I., Fenczik, C., Glembotski, C. C., Ginsberg, M. H., & Loftus, J. C. (1998). β Integrins participate in the hypertrophic response of rat ventricular myocytes. Circulation research, 82(11), 1160-1172. https://doi.org/10.1161/01.RES.82.11.1160