Platelet-derived endothelial cell growth factor inhibits DNA synthesis in vascular smooth muscle cells

Platelet-derived endothelial cell growth factor (PD-ECGF) is linked to angi ogenesis in human cancer. Direct studies have demonstrated that PD-ECGF is a potent mitogen for endothelial cells in vivo. Because endothelial repair and smooth muscle cell proliferation are two processes that affect arterial wall structure and tone, we analyzed the effects of PD-ECGF on DNA synthes is and creatine kinase BE-specific activity (CK) in human umbilical artery smooth muscle cells (SMC) and in a human umbilical endothelial cell line (E 304). In SMC, PD-ECGE (0.001 to 10 U/mL) inhibited DNA synthesis dose depen dently (-24% + 6% to -63% + 15%) assessed by (3)[H]thymidine incorporation into DNA, whereas in E304 it stimulated DNA synthesis dose dependently (30% + 4% to 100% + 4%). In both SMC and E304, however, PD-ECGF elicited an inc rease in CK-specific activity by 54% to 130% and 79% to 163%, respectively. These effects were reversed by a specific anti-PD-ECGF antibody. In E304 c ells PD-ECGF enhanced (17)beta-estradiol. (E-2) or dihydrotestosterone (DHT )induced DNA synthesis from 56% to 122% and from 127% to 359%, and CK activ ity from 70% to 180% and from 90% to 190%, respectively. in SMC PD-ECGF, an inhibitor of (3)[H]thymidine incorporation by itself, markedly enhanced th e stimulatory effect of low concentrations of E-2 and DHT on (3)[H]thymidin e incorporation. It also increased E-2 and DHT CK induction from 40% to 140 % and from 52% to 120%, respectively. In both E304 and SMC, PD-ECGF inhibit ed the proliferative and the CK-inducing effects of platelet-derived growth factor (PDGF) and immunoglobulin F-1 (IGF(1)). Thus, PD-ECGF, an establish ed growth promoter for endothelial cells, is a potent inhibitor of DNA synt hesis in human arterial SMC. However, in both E304 endothelial cells and SM C, PD-ECGF enhances the stimulatory effect of low concentrations of gonadal steroids on (3)[H]thymidine incorporation. PD-ECGF antagonizes PDGF- and I GF(1)-induced DNA synthesis in both E304 and SMC cells. By inhibiting arter ial SMC proliferation and accelerating endothelial cell replication PD-ECGF may buffer the effect of PDGF and favorably modulate arterial wall respons e to injury. Am J Hypertens 1999;12:882-889 (C) 1999 American Journal of Hy pertension, Ltd.