Mature adipocytes and perivascular adipose tissue stimulate vascular smooth muscle cell proliferation: effects of aging and obesity.

Adipocytes and perivascular adipose tissue are emerging as regulators of vascular function. The effects of adipocytes and perivascular adipose tissue on human smooth muscle cell (SMC) proliferation were investigated. Conditioned medium was prepared from cultured premature and differentiated 3T3-L1 adipocytes and from periaortic adipose tissue from young (3 mo) and old (24 mo) Wistar-Kyoto (WKY) rats, lean and obese Zucker rats (3 mo), and WKY rats fed normal chow or a high-fat diet for 3 mo. Conditioned medium from differentiated (but not premature) adipocytes stimulated SMC proliferation, which was abolished by charcoal and proteinase K treatment but was resistant to heat, trypsin, or phospholipase B (to hydrolyze lysophosphatidic acid). Further experiments demonstrated that the growth factor(s) are hydrosoluble and present in the fraction of molecular mass >100 kDa. Moreover, conditioned medium from periaortic adipose tissue stimulated SMC proliferation, which was significantly enhanced in aged rats and in rats fed a high-fat diet but not in obese Zucker rats deficient in functional leptin receptors. In conclusion, mature adipocytes release hydrosoluble protein growth factor(s) with a molecular mass >100 kDa for SMCs. Perivascular adipose tissue stimulates SMC proliferation, which is enhanced in aged WKY and in high-fat, diet-induced obesity but not in leptin receptor-deficient obese Zucker rats. These adipocyte-derived growth factor(s) and the effect of perivascular adipose tissue may be involved in vascular disease associated with aging and obesity.