THE INSULIN-LIKE GROWTH-FACTOR SYSTEM IN VASCULAR SMOOTH-MUSCLE - INTERACTION WITH INSULIN AND GROWTH-FACTORS

Vascular smooth muscle cells (SMCs) occur throughout the vascular tree and have important physiological functions. They are also involved in pathological processes such as development and progression of atheros clerotic lesions, restenosis following angioplasty, and in hypertensio n. This review is focused on the role of the insulin-like growth facto r (IGF) system in proliferation, migration, and hypertrophy of vascula r SMCs and its interaction with insulin and other growth factors. The IGF-I receptor is highly expressed in SMCs in intact arteries and in c ultured SMCs and is activated by binding of IGF-I to the two alpha-sub units. Insulin and IGF-II from the circulation can interact with the I GF-I receptor at higher concentrations, Insulin receptors are few or a bsent in SMCs and circulating insulin concentrations in vivo are proba bly too low for a direct action of insulin on the IGF-I receptor in SM Cs. Receptor activation initiates a number of signal transduction path ways. Increased phosphatidylinositol turnover and calcium mobilization correlates with actin filament reorganization and stimulation of dire cted migration of the SMC in a gradient of IGF-I. The effects of IGF-I receptor activation on signal transduction pathways (eg, the MAP kina se cascade) implicated in DNA synthesis and proliferation are weak and this correlates with the meager mitogenic activity of IGF-I in SMC, S everal components of the IGF-system in SMC are regulated by growth fac tors such as platelet derived growth factor (PDGF)-BB and basic fibrob last growth factor (bFGF). IGF-I is downregulated by decreased metabol ism (eg, diabetes and fasting) and in these states levels of IGF-I mRN A and IGFBP-2 and -4 mRNA are decreased. On the contrary, SMC hypertro phy is associated with increased levels of IGF-I, IGFBP-2, and IGFBP-4 mRNA. In conclusion, the IGF-system in SMCs is likely to play an impo rtant role in SMC migration and the response of the SMCs to metabolic deprivation, and hypertrophy. Copyright (C) 1995 by W.B. Saunders Comp any.