Smooth muscle cell proliferation in response to co-culture with venous and arterial endothelial cells

PURPOSE: The critical role of endothelial cells (ECs) in arterial disease is well established, but little is known of their role in venous disease, Previous studies suggest inherent differences between arteries and veins: arterial stenoses demonstrate a large lipid component, whereas hemodialysis-related venous stenoses are characterized by marked smooth muscle cell (SMC) proliferation, This study compares effects of venous versus arterial ECs on SMC proliferation in co-culture. MATERIALS AND METHODS: Human saphenous vein ECs (HSV-ECs) or human aortic ECs (HA-ECs) were cultured on the underside of 10-mu m, porous polycarbonate membranes and allowed to grow to confluence for 48 hours. After EC confluence, human aortic SMCs (HA-SMCs) were cultured on the membranes opposite the EC (day 0). On days 0, 1, 2, 4, 6, and 8, membranes were harvested (n = 3 per day), stained with Hoechst dye, and HA-SMCs were counted by fluorescence microscopy. Controls were HA-SMCs cultured alone. Comparisons were made by two-way multivariate analysis of variance. RESULTS: During the entire 8-day period, there was significant induction of HA-SMC proliferation by both HSV-ECs (P = .0003) and HA-ECs (P = .0012). Maxilraal inductions were 88% +/- 11% for HSV-ECs (P = .0015) and 24% +/- 6% for HA-ECs (P = .0015). HSV-ECs exhibited a three- to ninefold greater induction than HA-ECs (P = .0003). CONCLUSION: HSV-ECs induce adjacent HA-SMC proliferation, possibly in a paracrine manner to a significantly greater extent than HA-ECs.