Role of proto-oncogenes in myocardial hypertrophy

Abstract

A question of major clinical significance in cardiology is the nature of the signals that initiate and maintain the various types of myocardial hypertrophy, either in response to hemodynamic loading or in the absence of altered load. This review suggests that the proto-oncogene model, a concept derived from the study of cancer, can be very useful in identifying these signals. The proto-oncogene model conceives of cell growth regulation in terms of a limited number of classes of critical regulatory proteins: growth factors, growth factor receptors, intracellular transducing proteins and ribonucleic acid (RNA) transcription factors. Growth of all cells has dissociable components: hypertrophy (growth in size), deoxyribonucleic acid synthesis, mitosis and cytokinesis. Hypertrophy may be the end result of activation of RNA transcription. The various types of hypertrophy could reflect transcription of specific myocyte genes in response to different growth factors. At least 1 member of each functional class of proto-oncogenes has been detected in the myocardium or myocytes, or both. The α 1-adrenergic receptor has been shown to be a growth factor receptor and to regulate RNA transcription. Continued work on proto-oncogenes in myocytes may open the way to manipulate the growth of these cells.