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Insulin-Like Growth Factor-1 as a Vascular Protective Factor

Recent advances in cardiology have focused on proliferation and regeneration as potential cardiovascular defense mechanisms. Within this framework, growth factors are acquiring increasing importance; insulin-like growth factor-1 (IGF-1) emerges among them for its versatile pleiotropic actions. This review provides a current perspective on IGF-1 and vascular disease.

The IGF-1 system is dynamic and complex,1,2 involving at least 6 IGF-1–binding proteins (IGFBP-1 through -6) and several binding protein–related proteases,1 including pregnancy-associated plasma protein-A (PAPP-A). The latter promotes IGF-1 bioavailability by cleaving IGFBP-4 and -5.3 Acute coronary syndromes have been associated with raised PAPP-A concentrations in blood, leading to the interpretation that PAPP-A may enhance the risk of coronary artery disease through increased IGF-1 in vascular tissues.4 Recent results, however, suggest a different relation between IGF-1 and ischemic syndromes.

Indirect data have supported the concept that IGF-1 may be atherogenetic because it can induce vascular smooth muscle cell (VSMC) proliferation in vitro.5 Early studies on VSMCs from human and rabbit atherosclerotic arteries showed enhanced staining for IGF-1 and its receptor6,7 compared with normal tissues,7 with further enhancement after experimental angioplasty.7 Thus, IGF-1 has been considered a promoter of arterial obstructive lesions8; an alternative possibility, however (consistent with the higher IGF-1 expression after angioplasty), is that IGF-1 initiates a survival pathway aimed at compensating local vascular cell apoptosis (see sections III.C.3 and III.C.4).

Randomized trials of the somatostatin analogue, angiopeptin, have been performed in the setting of postangioplasty restenosis and heart transplant vasculopathy to assess the possible benefits of lowering IGF-1 levels.9 Somatostatin analogues, however, have multiple actions: They reduce growth hormone (GH) release and the serum concentrations of other growth factors (epidermal growth factor, fibroblast growth factor, platelet-derived growth factor, and vascular endothelial growth factor [VEGF]) in addition to IGF-1,10,11 …