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Objective-: We hypothesized that the hypoxia-inducible factor (HIF) 1[alpha] 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-HIF1[alpha]-/-, and ApoE-/-xsmooth muscle-HIF1[alpha]-/- 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 HIF1[alpha] from smooth muscle significantly reduced vascular inflammation, and attenuated atherosclerosis.

Conclusions-: HIF1[alpha] 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.

(C) 2016 American Heart Association, Inc.