AUTORADIOGRAPHIC MAPPING AND CHARACTERIZATION OF INSULIN-LIKE GROWTH FACTOR-I RECEPTOR-BINDING IN HUMAN GREATER SAPHENOUS-VEIN

Purpose: The proliferation of vascular smooth muscle cells is an impor tant step in the process of intimal hyperplasia. Veins exposed to arte rial pressure develop intimal hyperplastic lesions that lead to failur e of vein bypasses. Insulin-like growth factor-I is a polypeptide horm one structurally related to insulin with insulin-like metabolic effect s. Insulin-like growth factor-I has been found to work in concert with other growth factors, including platelet-derived growth factor, to pr omote the growth of vascular smooth muscle cells in culture. Insulin-l ike growth factor-I exerts its effects via specific receptors located on the cell surface. We studied the in situ distribution of insulin-li ke growth factor-I receptor binding using autoradiography and examined insulin-like growth factor-I binding characteristics in normal human greater saphenous vein. Methods: Frozen sections 20 mu m thick were pr epared from the greater saphenous vein specimens. The sections were in cubated in a buffer containing I-125-insulin-like growth factor-I in t he presence of increasing concentrations of the unlabeled peptide. Aut oradiograms were obtained by apposing the treated sections to autoradi ography film. Results: Analysis of the autoradiographs showed that ins ulin-like growth factor-I binding was consistently present in the wall of human greater saphenous vein. To characterize these binding sites binding inhibition studies were performed. High-affinity insulin-like growth factor-I receptor binding was found with dissociation constant of 1.0 +/- 0.32 nmol/L and maximum binding capacity of 0.46 +/- 0.23 p mol/mg protein. These values are consistent with a physiologic role fo r insulin-like growth factor-I in the tissue examined. Conclusions: Th e presence of high-affinity (dissociation constant = 1.0 +/- 0.32) ins ulinlike growth factor-I binding sites in the wall of saphenous vein s uggests that insulin-like growth factor-I plays an important role in r egulating the proliferation of venous wall cellular components, an ess ential step in the process of venous intimal hyperplasia.