Prolonged Hyperoxygenation Treatment Improves Vein Graft Patency and Decreases Macrophage Content in Atherosclerotic Lesions in ApoE3*Leiden Mice

Laura Parma, Hendrika A. B. Peters, Fabiana Baganha, Judith C. Sluimer, Margreet R. de Vries, Paul H. A. Quax*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Web of Science)

Abstract

Unstable atherosclerotic plaques frequently show plaque angiogenesis which increases the chance of rupture and thrombus formation leading to infarctions. Hypoxia plays a role in angiogenesis and inflammation, two processes involved in the pathogenesis of atherosclerosis. We aim to study the effect of resolution of hypoxia using carbogen gas (95% O-2, 5% CO2) on the remodeling of vein graft accelerated atherosclerotic lesions in ApoE3*Leiden mice which harbor plaque angiogenesis. Single treatment resulted in a drastic decrease of intraplaque hypoxia, without affecting plaque composition. Daily treatment for three weeks resulted in 34.5% increase in vein graft patency and increased lumen size. However, after three weeks intraplaque hypoxia was comparable to the controls, as were the number of neovessels and the degree of intraplaque hemorrhage. To our surprise we found that three weeks of treatment triggered ROS accumulation and subsequent Hif1a induction, paralleled with a reduction in the macrophage content, pointing to an increase in lesion stability. Similar to what we observed in vivo, in vitro induction of ROS in bone marrow derived macrophages lead to increased Hif1a expression and extensive DNA damage and apoptosis. Our study demonstrates that carbogen treatment did improve vein graft patency and plaque stability and reduced intraplaque macrophage accumulation via ROS mediated DNA damage and apoptosis but failed to have long term effects on hypoxia and intraplaque angiogenesis.

Original languageEnglish
Article number336
Number of pages18
JournalCells
Volume9
Issue number2
DOIs
Publication statusPublished - Feb 2020

Keywords

  • hyperoxygenation
  • vein graft disease
  • atherosclerosis
  • macrophages
  • vascular biology
  • NF-KAPPA-B
  • HYPOXIA-INDUCIBLE FACTOR
  • HYPEROXIA
  • CARBOGEN
  • OXYGEN
  • HIF-1-ALPHA
  • ACTIVATION
  • MECHANISMS
  • EXPRESSION
  • APOPTOSIS

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