TY - JOUR
T1 - Arginase inhibition enhances angiogenesis in endothelial cells exposed to hypoxia
AU - Wang, Lin
AU - Bhatta, Anil
AU - Flores Toque, Haroldo Alfredo
AU - Rojas, Modesto Antonio
AU - Yao, Lin
AU - Xu, Zhimin
AU - Patel, Chintan
AU - Caldwell, Ruth B
AU - Caldwell, Robert William
N1 - Publisher Copyright:
© 2014 Elsevier Inc.
PY - 2015/3/1
Y1 - 2015/3/1
N2 - 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-eNOSSer1177 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.
AB - 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-eNOSSer1177 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.
KW - Angiogenesis
KW - Arginase
KW - Endothelial cell
KW - Endothelial nitric oxide synthase (eNOS)
KW - Reactive oxygen species (ROS)
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U2 - 10.1016/j.mvr.2014.11.002
DO - 10.1016/j.mvr.2014.11.002
M3 - Article
C2 - 25445030
AN - SCOPUS:84924856530
SN - 0026-2862
VL - 98
SP - 1
EP - 8
JO - Microvascular Research
JF - Microvascular Research
ER -