Effects of insulin-like growth factor-I on cultured human coronary artery smooth muscle cells

The growth-promoting effects of insulin-like growth factor-I (IGF-I) appear to be different in vascular smooth muscle cells from various segments of the arterial tree. Little information exists on human coronary artery smooth muscle cells (CoSMC), the primary elements of coronary atherosclerosis and post-angioplasty restenosis. In this study we determined the effects of IGF-I on cultured human CoSMC. Type I IGF receptors (IGF-R) were present on CoSMC as assessed by affinity cross-linking of ¹²⁵I-IGF-I to monolayer cultures. IGF-I was a weak mitogen, 1.5-fold increase in [³H]thymidine incorporation, for CoSMC. However, IGF-I had a potent motility effect on CoSMC with a 314 ± 12% increase in cell migration (P < 0.001), comparable to that of 5% FBS. IGF-I-stimulated motility was partially inhibited by αIR-3, a specific IGF-R inhibitor (P < 0.05). Addition of kistrin, a disintegrin, or LM609, a specific α_vβ₃ integrin neutralizing antibody, abolished IGF-I-stimulated migration (P < 0.001). This study indicates that IGF-I is a potent motility agent for human CoSMC via the α_vβ₃ integrin receptor, but exerts little mitogenic effect. Because CoSMC migration plays a crucial role in atherosclerosis and restenosis, IGF-I blockade has the potential to limit lumen reduction.