INDUCTION OF INSULIN-LIKE GROWTH FACTOR-I MESSENGER-RNA IN RAT AORTA AFTER BALLOON DENUDATION

Insulin-like growth factor I (IGF-I) is a widely distributed mitogen that mediates the growth-promoting effects of platelet-derived growth factor in mesenchymal cells. We show that rat aortic IGF-I messenger RNA (mRNA) is induced 24 hours after deendothelialization, at a time when smooth muscle cell proliferation within the intima is still not apparent. After 7 days, IGF-I mRNA induction peaks at about ninefold control levels and then falls to about threefold 14 days after denudation when smooth muscle cell proliferation is at its peak. We also show that, of the 5' untranslated IGF-I mRNA transcripts, only the class C transcript is expressed and regulated in aortic tissue. In contrast, treatment of rats with supraphysiological doses of growth hormone, the major endocrine regulator of IGF-I gene expression, elicited only twofold induction of aortic IGF-I mRNA. Our findings suggest that IGF-I may be an important autocrine or paracrine regulator of smooth muscle cell proliferation and that it may be significant in determining the cellular response to arterial wall injury.