Interactions of arterial cells. Studies on the mechanisms of endothelial cell modulation of cholesterol metabolism in co-cultured smooth muscle cells.
Academic Article
Overview
abstract
Fluid phase interactions between arterial endothelial cells (EC) and smooth muscle cells (SMC) have been studied in vitro to assess the regulation of lipid metabolism in SMC (Hajjar, D. P., Falcone, D. J., Amberson, J. B., and Hefton, J. M. (1985) J. Lipid Res. 26, 1212-1223; Davies, P. F., Truskey, G. A., Warren, H. B., O'Connor, S. E., and Eisenhaure, B. H. (1985) J. Cell Biol. 101, 871-879). To identify EC-derived agonists which may modulate cholesterol metabolism in co-cultured SMC, we assessed the role of EC-derived eicosanoids and platelet-derived growth factor (PDGF) in the regulation of cholesteryl ester (CE) hydrolysis in SMC. The major eicosanoids synthesized by EC include PGI2 and 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) and, to a lesser extent, prostaglandin E2. Exogenously added PGI2 and 12-HETE stimulated CE hydrolytic activity in SMC by 49 and 35%, respectively, when co-cultured with aspirin-treated EC. Aspirin-treated EC when co-cultured with SMC did not stimulate CE hydrolytic activity in SMC, as was the case with non-aspirin-treated EC, suggesting a role of eicosanoids in the regulation of cholesterol metabolism. Other humoral agents derived from EC such as PDGFc stimulated CE hydrolytic activity almost 2-fold in SMC cultured alone or co-cultured with EC. Aspirin-treated EC, incubated with 10 ng/ml PDGF, did not stimulate CE hydrolytic activity in co-cultured SMC. These results suggest that growth factor-promoting activity may enhance CE hydrolysis via the PGI2-cyclic AMP-CE hydrolysis cascade. This hypothesis supports our observations that PDGF stimulates PGI2 production in SMC. Elevated PGI2, in turn, can stimulate CE hydrolysis in these cells. Our findings suggest that the regulation of cholesterol metabolism in SMC can involve, at least in part, growth factors and EC-derived eicosanoids. These may play a central role in the regulation of hemostasis and the inflammatory response.
