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 alphaIR-3, a specific IGF-R inhibitor (P<0.05). Addition of kistrin, a disintegrin, or LM609, a specific alpha(V)beta(3) 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 alpha(V)beta(3) 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.
Bayes-Genis
Antoni
A
Division of Cardiovascular Diseases and Endocrine Research Unit , Mayo Clinic and Foundation, 200 First Street SW, 5-194 Joseph, Rochester, MN 55905, USA.
Schwartz
Robert S
RS
Bale
Laurie K
LK
Conover
Cheryl A
CA
D002465:Cell Movement; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects; D017526:Receptor, IGF Type 1 / Q000378:metabolism
D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1