Hyperbaric oxygen activates visfatin expression and angiogenesis via angiotensin II and JNK pathway in hypoxic human coronary artery endothelial cells

J Cell Mol Med. 2020 Feb;24(4):2434-2443. doi: 10.1111/jcmm.14926. Epub 2020 Jan 19.

Abstract

Visfatin is an adipocytokine with important roles in endothelial angiogenesis. Hyperbaric oxygen (HBO) has been widely used to treat various medical illness with enhanced angiogenesis. The molecular effects of HBO on visfatin under hypoxia are poorly understood. This study aimed to investigate the effect of HBO on visfatin in hypoxic human coronary arterial endothelial cells (HCAECs). HCAECs under chemical hypoxia (antimycin A, 0.01 mmol/L) were exposed to HBO (2.5 atmosphere absolute; ATA) for 2-4 hours. Western blot, real-time polymerase chain reaction, electrophoretic mobility shift assay, luciferase promoter activity, migration and tube formation assay, and in vitro glucose uptake were measured. Visfatin protein expression increased in hypoxic HCAECs with earlier angiotensin II (AngII) secretion and c-Jun N-terminal kinase (JNK) phosphorylation, which could be effectively suppressed by the JNK inhibitor (SP600125), AngII antibody or AngII receptor blocker (losartan). In hypoxic HCAECs, HBO further induced earlier expression of visfatin and AngII. Hypoxia significantly increased DNA-protein binding activity of hypoxia-inducible factor-1α (HIF-1α) and visfatin. Hypoxia, hypoxia with HBO and exogenous addition of AngII also increased promoter transcription to visfatin; SP600125 and losartan blocked this activity. In HCAECs, glucose uptake, migration and tube formation were increased in the presence of hypoxia with HBO, but were inhibited by visfatin small interfering RNA, SP600125 and losartan. In conclusion, HBO activates visfatin expression and angiogenesis in hypoxic HCAECs, an effect mediated by AngII, mainly through the JNK pathway.

Keywords: adipocytokine; angiogenesis; hyperbaric oxygen; hypoxia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / metabolism*
  • Anthracenes / pharmacology
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cells, Cultured
  • Coronary Vessels / drug effects
  • Coronary Vessels / metabolism*
  • Cytokines / metabolism*
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism*
  • Glucose / metabolism
  • Humans
  • Hyperbaric Oxygenation / methods
  • Hypoxia / metabolism
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Losartan / pharmacology
  • Neovascularization, Pathologic / metabolism*
  • Nicotinamide Phosphoribosyltransferase / metabolism*
  • Oxygen / metabolism*
  • Promoter Regions, Genetic / drug effects
  • Promoter Regions, Genetic / genetics
  • RNA, Small Interfering / genetics
  • Signal Transduction / drug effects
  • Signal Transduction / physiology

Substances

  • Anthracenes
  • Cytokines
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • RNA, Small Interfering
  • Angiotensin II
  • pyrazolanthrone
  • Nicotinamide Phosphoribosyltransferase
  • nicotinamide phosphoribosyltransferase, human
  • JNK Mitogen-Activated Protein Kinases
  • Glucose
  • Losartan
  • Oxygen