Autoradiographic mapping and characterization of insulin-like growth factor-I receptor binding in human greater saphenous vein.
OBJECTIVE
The proliferation of vascular smooth muscle cells is an important step in the process of intimal hyperplasia. Veins exposed to arterial pressure develop intimal hyperplastic lesions that lead to failure of vein bypasses. Insulin-like growth factor-I is a polypeptide hormone structurally related to insulin with insulin-like metabolic effects. Insulin-like growth factor-I has been found to work in concert with other growth factors, including platelet-derived growth factor, to promote the growth of vascular smooth muscle cells in culture. Insulin-like growth factor-I exerts its effects via specific receptors located on the cell surface. We studied the in situ distribution of insulin-like 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 microns thick were prepared from the greater saphenous vein specimens. The sections were incubated in a buffer containing 125I-insulin-like growth factor-I in the presence of increasing concentrations of the unlabeled peptide. Autoradiograms were obtained by apposing the treated sections to autoradiography film.


RESULTS
Analysis of the autoradiographs showed that insulin-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 pmol/mg protein. These values are consistent with a physiologic role for insulin-like growth factor-I in the tissue examined.


CONCLUSIONS
The presence of high-affinity (dissociation constant = 1.0 +/- 0.32) insulin-like growth factor-I binding sites in the wall of saphenous vein suggests that insulin-like growth factor-I plays an important role in regulating the proliferation of venous wall cellular components, an essential step in the process of venous intimal hyperplasia.
Sidawy
A N
AN
Department of Surgery, Veterans Affairs Medical Center, Washington, DC 20422.
Hakim
F S
FS
Neville
R F
RF
Korman
L Y
LY
D001345:Autoradiography; D001665:Binding Sites; D002455:Cell Division; D002478:Cells, Cultured; D003720:Densitometry; D005629:Frozen Sections; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007457:Iodine Radioisotopes; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D012501:Saphenous Vein / Q000166:cytology / Q000378:metabolism*
D007457:Iodine Radioisotopes; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1