title: Endostatin induces acute endothelial nitric oxide and prostacyclin release.
abstract: Chronic exposure to endostatin (ES) blocks endothelial cell (EC) proliferation, and migration and induces EC apoptosis thereby inhibiting angiogenesis. Nitric oxide (NO) and prostacyclin (PGI(2)), in contrast, play important roles in promoting angiogenesis. In this study, we examined the acute effects of ES on endothelial NO and PGI(2) production. Unexpectedly, a cGMP reporter cell assay showed that ES-induced acute endothelial NO release in cultured bovine aortic endothelial cells (BAECs). Enzyme immunoassay showed that ES also induced an acute increase in PGI(2) production in BAECs. These results were confirmed by ex vivo vascular ring studies that showed vascular relaxation in response to ES. Immunoblot analysis showed that ES stimulated acute phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser116, Ser617, Ser635, and Ser1179, and dephosphorylation at Thr497 in BAECs, events associated with eNOS activation. Short-term exposure of EC to ES, therefore, unlike long-term exposure which is anti-angiogenic, may be pro-angiogenic.
authors.affiliation: Vascular Biology Center, Medical College of Georgia, Augusta, GA 30912, USA.
authors.forename: Chunying
authors.initials: C
authors.lastname: Li
authors.forename: M Brennan
authors.initials: MB
authors.lastname: Harris
authors.forename: Virginia J
authors.initials: VJ
authors.lastname: Venema
authors.forename: Richard C
authors.initials: RC
authors.lastname: Venema
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D043169:Endostatins / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III
chemical_list: D043169:Endostatins; D009569:Nitric Oxide; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III