Insulin-like growth factor I and its binding proteins in the cardiovascular system.

A large body of evidence has conclusively shown that IGF I is an essential regulator of developmental growth. Thus mice bearing a null mutation for the IGF IR gene invariably die shortly after birth, and mice bearing a null mutation for the IGF I gene have a high neonatal mortality rate and marked growth retardation [158,159]. The ubiquitous effects of IGF I make it likely that this autocrine/endocrine system plays an important role in cardiovascular development. Its potential role in cardiovascular pathophysiology has raised considerable interest over the last several years. There is strong evidence that IGF I is a critical determinant of vascular growth responses in vitro and in vivo. Regulation of VSMC IGF IR availability appears to be crucial for the control of VSMC growth, and as such is at a convergence point for the effects of multiple growth factors. Clinical studies relating to IGF I in hypertension are extremely limited but significant data from animal studies now suggest a role for IGF I as a mediator of hypertrophic/hyperplastic responses in hypertension. Furthermore, significant animal data now exist implicating IGF I as an important mediator of cardiac hypertrophic responses. The development of a specific pharmacologic inhibitor of the IGF IR should allow rational clinical trials to address the function of IGF I as a mediator of cardiovascular growth responses. Specifically, areas of great interest will include the potential prevention of post-angioplasty restenosis, of atherosclerotic lesion development and progression, and of the complications of hypertensive vascular disease. The use of IGF I to ameliorate myocardial growth and function post infarction, to promote angiogenesis and collateral artery formation in the setting of peripheral vascular disease, are other important directions for future research. The use of IGF I to improve wound healing, improve recovery from acute renal failure and improve glucose control is currently under investigation. Clearly ongoing studies addressing the mechanisms whereby IGF I interacts with its receptor and binding proteins to produce its effects in cardiovascular tissues, will provide a rationale for novel and pertinent clinical research.