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.

journal_name

Microvasc Res

journal_title

Microvascular research

authors

Wang L,Bhatta A,Toque HA,Rojas M,Yao L,Xu Z,Patel C,Caldwell RB,Caldwell RW

doi

10.1016/j.mvr.2014.11.002

subject

Has Abstract

pub_date

2015-03-01 00:00:00

pages

1-8

eissn

0026-2862

issn

1095-9319

pii

S0026-2862(14)00170-8

journal_volume

98

pub_type

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