Cardiac hypertrophy and related growth processes: the role of insulin-like growth factor-I.

For the heart and resistance vessels in general, increases in pressure load represent a major local stimulus for structural adaptation by elevating the wall tension against which cardiac and vascular smooth muscle contract. Under such conditions the wall thickness of the left ventricle and of the resistance vessels will increase, keeping wall tension per unit muscle layer (wall stress) normal. Alternatively, chronic volume overload and enhanced cardiac filling will induce a structurally based widening of the ventricular lumen. This pattern is associated with a corresponding increase in myocardial mass, so that the wall thickness to internal radius ratio remains more or less constant. A number of extrinsic influences such as the sympathetic nervous system, hormonal factors and growth factors, may superimpose their effects to modulate the final "trophic influence" on the cardiovascular system. Hyperactivity of the renin-angiotensin system, the sympathetic nervous system and various growth factors, have all been suggested to initiate cardiovascular growth in a way that is load-independent. The mechanisms involved in the conversion of a mechanical hypertrophic stimulus into an actual increase in tissue mass are likely to involve many substances and enzyme systems, including transcription factors, enzymes such as ornithine decarboxylase and various growth factors. The presence of the insulin-like growth factor-I (IGF-I) in the heart and vessels suggests a paracrine/autocrine role for this potent growth factor in the regulation of cardiovascular growth. The relationships between ornithine decarboxylase, cardiovascular hypertrophy and IGF-I gene expression are also reviewed.