Arginase inhibition enhances angiogenesis in endothelial cells exposed to hypoxia

Lin Wang, Anil Bhatta, Haroldo Alfredo Flores Toque, Modesto Antonio Rojas, Lin Yao, Zhimin Xu, Chintan Patel, Ruth B Caldwell, Robert William Caldwell

Research output: Contribution to journalArticle

12 Scopus citations

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-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.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalMicrovascular Research
Volume98
DOIs
StatePublished - Mar 1 2015

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine
  • Cell Biology

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