Contraction-induced cell wounding and release of fibroblast growth factor in heart

M. S F Clarke, R. W. Caldwell, H. Chiao, K. Miyake, P. L. McNeil

Research output: Contribution to journalArticle

165 Scopus citations

Abstract

The heart hypertrophies in response to certain forms of increased mechanical load, but it is not understood how, at the molecular level, the mechanical stimulus of increased load is transduced into a cell growth response. One possibility is that mechanical stress provokes the release of myocyte-derived autocrine growth factors. Two such candidate growth factors, acidic and basic fibroblast growth factor (aFGF and bFGF, respectively), are released via mechanically induced disruptions of the cell plasma membrane. In the present study, we demonstrate that transient, survivable disruption (wounding) of the cardiac myocyte plasma membrane is a constitutive event in vivo. Frozen sections of normal rat heart were immunostained to reveal the distribution of the wound event marker, serum albumin. Quantitative image analysis of these sections indicated that an average of 25% of the myocytes contained cytosolic serum albumin; ie, this proportion had suffered a plasma membrane wound. Wounding frequency increased approximately threefold after β-adrenergic stimulation of heart rate and force of contraction. Heparin- Sepharose chromatography, enzyme-linked immunosorbent assay, growth assay coupled with antibody neutralization, and two-dimensional SDS-PAGE followed by immunoblotting were used to demonstrate that both aFGF and bFGF were released from an ex vivo heating rat heart. Importantly, β-adrenergic stimulation of heart rate and force of contraction increased FGF release. Cell wounding is a fundamental but previously unrecognized aspect of the biology of the cardiac myocyte. We propose that contraction-induced cardiac myocyte wounding releases aFGF and bFGF, which then may act as autocrine growth-promoting stimuli.

Original languageEnglish (US)
Pages (from-to)927-934
Number of pages8
JournalCirculation research
Volume76
Issue number6
DOIs
StatePublished - Jun 1995

Keywords

  • cell injury
  • fibroblast growth factor
  • heart hypertrophy
  • myocardium
  • plasma membrane

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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