Paracrine effect of human vascular endothelial cells on human vascular smooth muscle cell proliferation: transmembrane co-culture method.

To investigate the role endothelial cells have on underlying smooth muscle cell proliferation, human aortic vascular smooth muscle cells were co-cultured with human aortic endothelial cells at different cell densities, using a transmembrane co-culture method. Subconfluent endothelial cells subseeded at low (0.5 x 10(4) cells/well) and medium densities (2.0 x 10(4) cells/well) stimulated smooth muscle cell proliferation by 43 +/- 14% (P < 0.01) and 39 +/- 8% (P < 0.02), respectively. However, this stimulatory effect on smooth muscle cell proliferation was not evident in confluent endothelial cells subseeded at high cell density (8.0 x 10(4) cells/well). Treatment of smooth muscle cells with trapidil, at 10(-6) M, for anti-platelet derived growth factor (PDGF) effect or with endothelin-1 receptor blocker FR 139317, at 10(-6) M failed to inhibit this stimulatory effect. These results imply that subconfluent human endothelial cells are able to exert a stimulatory effect on human smooth muscle cell proliferation, and that this endothelial paracrine growth effect may not be mediated by endothelin or PDGF.