Smooth Muscle Hypoxia-Inducible Factor 1α Links Intravascular Pressure and Atherosclerosis--Brief Report

Arterioscler Thromb Vasc Biol. 2016 Mar;36(3):442-5. doi: 10.1161/ATVBAHA.115.306861. Epub 2016 Jan 21.

Abstract

Objective: We hypothesized that the hypoxia-inducible factor (HIF) 1α in vascular smooth muscle contributes to the development of atherosclerosis, and links intravascular pressure to this process.

Approach and results: Transverse aortic constriction was used to create high-pressure vascular segments in control, apolipoprotein E (ApoE)(-/-), smooth muscle-HIF1α(-/-), and ApoE(-/-)×smooth muscle-HIF1α(-/-) double-knockout mice. Transverse aortic constriction selectively induced atherosclerosis in high-pressure vascular segments in young ApoE(-/-) mice on normal chow, including coronary plaques within 1 month. Concomitant deletion of HIF1α from smooth muscle significantly reduced vascular inflammation, and attenuated atherosclerosis.

Conclusions: HIF1α in vascular smooth muscle plays an important role in the pathogenesis of atherosclerosis, and may provide a mechanistic link between blood pressure, vascular inflammation, and lipid deposition.

Keywords: atherosclerosis; blood pressure; hypoxia-inducible factor; inflammation; smooth muscle.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Aorta / metabolism
  • Aorta / physiopathology
  • Aortic Diseases / genetics
  • Aortic Diseases / metabolism*
  • Aortic Diseases / pathology
  • Aortic Diseases / physiopathology
  • Aortic Diseases / prevention & control
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics
  • Arterial Pressure*
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism*
  • Atherosclerosis / pathology
  • Atherosclerosis / physiopathology
  • Atherosclerosis / prevention & control
  • Blood Flow Velocity
  • Diet, High-Fat
  • Disease Models, Animal
  • Gene Expression Regulation
  • Hypoxia-Inducible Factor 1, alpha Subunit / deficiency
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Ligation
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Smooth, Vascular / metabolism*
  • Muscle, Smooth, Vascular / pathology
  • Muscle, Smooth, Vascular / physiopathology
  • Muscle, Smooth, Vascular / surgery
  • Plaque, Atherosclerotic
  • Regional Blood Flow
  • Signal Transduction
  • Time Factors

Substances

  • Apolipoproteins E
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit