Regulation of insulin-like growth factor-I and its receptor in rat aorta after balloon denudation. Evidence for local bioactivity.
Local production of growth factors may play a major role in vascular repair after injury. We examined the regulation of insulin-like growth factor-I (IGF-I) and its specific membrane receptor in balloon-denuded rat aorta. Aortic IGF-I mRNA and radioimmunoassayable IGF-I content increased severalfold after balloon denudation with a peak at 7 d after injury. This coincided with a reciprocal 25% decrease in IGF-I receptor mRNA content and a 40% decrease in total 125I-IGF-I binding. Scatchard analysis indicated a single class of binding sites, with a decrease in receptor number at 7 d compared to control and no change in affinity. By in situ hybridization the predominant site of IGF-I expression in the normal and the denuded vessel wall was the medial smooth muscle cell. After denudation there was a relative decrease in IGF-I receptor mRNA in the medial cells as compared to the neointima, suggesting that the site of IGF-I action was predominantly in the medial layer. These data suggest that local expression and action of IGF-I are significant in the promotion of smooth muscle cell proliferation after arterial injury.
Khorsandi
M J
MJ
Division of Cardiology, Cedars-Sinai Medical Center, Los Angeles, California 90048-1896.
Fagin
J A
JA
Giannella-Neto
D
D
Forrester
J S
JS
Cercek
B
B
D000818:Animals; D001011:Aorta / Q000378:metabolism; D002404:Catheterization; D002455:Cell Division; D005786:Gene Expression Regulation; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000235:genetics*
D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1