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

Dinggang Liu, Li Lei, Matthew Desir, Yan Huang, Jacob Cleman, Weidong Jiang, Carlos Fernandez-Hernando, Annarita Di Lorenzo, William C Sessa, Frank J Giordano
Arteriosclerosis, Thrombosis, and Vascular Biology 2016, 36 (3): 442-5

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.

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