Alprostadil suppresses angiogenesis in vitro and in vivo in the murine Matrigel plug assay

1 Prostaglandin E-1 (PGE(1), alprostadil) is used as a vasodilator for the treatment of peripheral vascular diseases. 2 Previous reports suggested a pro-angiogenic effect for PGE(1). 3 We studied the in vitro and in vivo effect of PGE(1), complexed with alpha-cyclodextrin, on the angiogenic process. Contrary to what was expected, we found that, in human umbilical vein endothelial cells (HUVECs), PGE(1) inhibited proliferation, migration and capillary-like structure formation in Matrigel. 4 By RT-PCR studies, the expression of the EP2 and EP3 subtypes of the PG receptor was detected in HUVECs. 5 PGE(1) alone stimulated adenylate cyclase activity at micromolar concentrations, while at nanomolar concentrations potentiated the forskolin-induced cAMP accumulation. 6 8-Bromoadenosine-3':5'-cyclic monophosphate (Br-cAMP) mimicked the inhibitory effect of PGE(1) on endothelial cell growth, motility and tube formation. 7 Sulprostone, an agonist at the EP3 subtype of PG receptors, mimicked the in vitro anti-angiogenic effects of PGE(1), while butaprost, an EP2 receptor agonist, had no effect. 8 Finally, in the plug assay model of angiogenesis in mice, PGE(1) showed a strong inhibitory effect on Matrigel neovascularization. 9 Thus, PGE(1) possesses strong anti-angiogenic activity in vitro and in vivo.