Modulation of cardiac genes by mechanical stress. The oncogene signalling hypothesis.

Abstract

In cardiac muscle, the selectivity and specificity of gene regulation by heparin-binding and transforming growth factors resembles the characteristic program of fetal gene induction during myocardial hypertrophy produced by load. Shared by isolated cardiac myocytes and intact hearts, these complex and heterogeneous responses provide intriguing systems, which are distinct from other lineages and models of cell growth, for the study of trophic signal transduction by cellular oncogenes. A functional role for peptide growth factors and other oncogene-encoded proteins in myocardial hypertrophy suggests biological pathways which might usefully be exploited to promote compensatory growth following infarction or to interfere with maladaptive changes during a hemodynamic load.