Angiotensin II Modulation of Insulin-like Growth Factor I Expression in the Cardiovascular System

The renin-angiotensin system is important in the pathophysiology of hypertension, cardiac hypertrophy, heart failure, and vascular remodeling. Angiotensin II is a growth factor for vascular smooth muscle cells and for cardiac myocytes and non-myocytes. Recently, angiotensin II has been shown to interact at multiple levels with the insulin-like growth factor I (IGF-I) system. IGF-I is a major regulator of developmental growth, and of cellular metabolism and differentiation, acting by endocrine and autocrine/paracrine pathways. Angiotensin II activates IGF-I receptor signaling through multiple mechanisms, and this activation is required for the growth-promoting effects of angiotensin II on vascular smooth muscle. Angiotensin II also stimulates cardiac IGF-I gene expression. Contrary to its effects on vascular and cardiac IGF-I expression, angiotensin II depresses circulating IGF-I through a pressor-independent anorexigenic effect. The anorexigenic effect of angiotensin II, and an additional metabolic effect, produce marked weight loss in the angiotensin II-infused animal. The alterations in local and circulating IGF-I expression produced by angiotensin II are potentially of importance in understanding the pathophysiology of conditions in which the renin-angiotensin system is activated. (Trends Cardiovascular Med 1996;6:187-193).