Arginase inhibition enhances angiogenesis in endothelial cells exposed to hypoxia

作者：Wang, Lin; Bhatta, Anil; Toque, Haroldo A.; Rojas, Modesto; Yao, Lin; Xu, Zhimin; Patel, Chintan; Caldwell, Ruth B.; Caldwell, R. William

来源：Microvascular Research, 2015, 98: 1-8.

DOI：10.1016/j.mvr.2014.11.002

• Arginase
• Reactive oxygen species (ROS)
• Endothelial nitric oxide synthase (eNOS)
• Angiogenesis
• Endothelial cell

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 24 h 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.

• 出版日期2015-3
• 单位上海交通大学