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.