Smooth muscle hypoxia-inducible factor 1α links intravascular pressure and atherosclerosis-brief report

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.