The insulin-like growth factors: their putative role in atherogenesis

Smooth muscle cell proliferation and leukocyte infiltration are characteristic features of all lesions of atherosclerosis. Although platelet derived growth factor (PDGF) is one of the major smooth muscle mitogens, other important mitogenic factors are found in plasma and in platelets. The insulin-like growth factors (IGF-I and IGF-II) are present in plasma complexed to one of a number of IGF-binding proteins (IGF-BP). They are also found at high concentrations within the alpha-granules of platelets. The IGFs are secreted by a number of cell types in-vitro and in-vivo, including smooth muscle cells and macrophages. The cellular effects of the IGFs are mediated by membrane bound high affinity receptors. IGF receptors are of two distinct types and are expressed by a wide variety of cells. The IGFs are potent smooth muscle cell mitogens and it is therefore possible that these polypeptides contribute to the formation of the atherosclerotic lesion by paracrine, autocrine or endocrine mechanisms.