title: Arginase inhibition enhances angiogenesis in endothelial cells exposed to hypoxia.
abstract: Hypoxia-induced arginase elevation plays an essential role in several vascular diseases but influence of arginase on hypoxia-mediated angiogenesis is completely unknown. In this study, in vitro network formation in bovine aortic endothelial cells (BAEC) was examined after exposure to hypoxia for 24h with or without arginase inhibition. Arginase activity, protein levels of the two arginase isoforms, eNOS, and VEGF as well as production of NO and ROS were examined to determine the involvement of arginase in hypoxia-mediated angiogenesis. Hypoxia elevated arginase activity and arginase 2 expression but reduced active p-eNOS(Ser1177) and NO levels in BAEC. In addition, both VEGF protein levels and endothelial elongation and network formation were reduced with continued hypoxia, whereas ROS levels increased and NO levels decreased. Arginase inhibition limited ROS, restored NO formation and VEGF expression, and prevented the reduction of angiogenesis. These results suggest a fundamental role of arginase activity in regulating angiogenic function.
authors.affiliation: Department of Plastic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China; Department of Pharmacology and Toxicology, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Toxicology, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Anil
authors.initials: A
authors.lastname: Bhatta
authors.affiliation: Department of Pharmacology and Toxicology, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Haroldo A
authors.initials: HA
authors.lastname: Toque
authors.affiliation: Vascular Biology Center, Georgia Regents University, Charlie Norwood VA Medical Center, Augusta GA, 30912, USA.
authors.forename: Modesto
authors.initials: M
authors.lastname: Rojas
authors.affiliation: Department of Pharmacology and Toxicology, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Yao
authors.affiliation: Vascular Biology Center, Georgia Regents University, Charlie Norwood VA Medical Center, Augusta GA, 30912, USA.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Vascular Biology Center, Georgia Regents University, Charlie Norwood VA Medical Center, Augusta GA, 30912, USA.
authors.forename: Chintan
authors.initials: C
authors.lastname: Patel
authors.affiliation: Vascular Biology Center, Georgia Regents University, Charlie Norwood VA Medical Center, Augusta GA, 30912, USA.
authors.forename: Ruth B
authors.initials: RB
authors.lastname: Caldwell
authors.affiliation: Department of Pharmacology and Toxicology, Georgia Regents University, Augusta, GA 30912, USA. Electronic address: wcaldwel@gru.edu.
authors.forename: R William
authors.initials: RW
authors.lastname: Caldwell
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000201:enzymology; D001119:Arginase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002417:Cattle; D015687:Cell Hypoxia; D042783:Endothelial Cells / Q000201:enzymology*; D004730:Endothelium, Vascular / Q000201:enzymology; D000860:Hypoxia / Q000473:pathology*; D009389:Neovascularization, Pathologic; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D001119:Arginase
keywords: Angiogenesis; Arginase; Endothelial cell; Endothelial nitric oxide synthase (eNOS); Reactive oxygen species (ROS)