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Objective: Adipocytes are highly active in releasing vasoactive hormones. We investigated effects of adipocytes and perivascular adipose tissue on vascular smooth muscle cell (SMC) proliferation in obesity and aging.
Methods and Results: Conditioned medium was prepared from cultured premature and differentiated 3T3-L1 adipocytes (cell number matched), from peri-aortic adipose tissue (adipose tissue weight matched) of young (3 months) and old (24 months) WKY rats or from lean and obese Zucker rats (3 months). Conditioned medium from differentiated (but not premature) adipocytes stimulated SMC proliferation (maximum: 206±21% increase), which was resistant to heat, trypsin or phospholipase B (to hydrolyse lysophosphatidic acid), although over 70 to 90% of inhibition of p42/44mapk stimulated by the conditioned medium were achieved under these treatments. In contrast to trypsin, proteinase K abolished the growth stimulatory effect of conditioned medium. Further experiments demonstrated that the growth factor(s) is present in the hydrosoluble fraction of the condition medium and has a molecular weight higher than 100 kDa. Moreover, conditioned medium from peri-aortic adipose tissue stimulated SMC proliferation, which was significantly enhanced in aged rats, but not in obese Zucker rats.
Conclusions: Mature adipocytes release a so far uncharacterized SMC growth factor(s) with a molecular weight higher than 100 kDa. The factor(s) is heat- and trypsin-resistant, but proteinase K-sensitive. Perivascular adipose tissue stimulates SMC proliferation, which is enhanced in aged WKY, but not in obese Zucker fa/fa rats. This adipocyte-derived SMC growth factor(s) may be involved in vascular remodeling under certain pathological conditions.
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