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

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

Author information

1
From the Departments of Medicine (D.L., L.L., M.D., Y.H., J.C., W.J., F.J.G.) and Pharmacology (W.C.S.), Yale University, New Haven, CT; Department of Pathology, NYU Langone Medical Center, New York, NY (C.F.-H.); and Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY (A.D.L.).
2
From the Departments of Medicine (D.L., L.L., M.D., Y.H., J.C., W.J., F.J.G.) and Pharmacology (W.C.S.), Yale University, New Haven, CT; Department of Pathology, NYU Langone Medical Center, New York, NY (C.F.-H.); and Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY (A.D.L.). frank.giordano@yale.edu.

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

PMID:
26800562
DOI:
10.1161/ATVBAHA.115.306861
[Indexed for MEDLINE]

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