Smooth Muscle Hypoxia-Inducible Factor 1[alpha] Links Intravascular Pressure and Atherosclerosis-Brief Report.
Liu, Dinggang; Lei, Li; Desir, Matthew; Huang, Yan; Cleman, Jacob; Jiang, Weidong; Fernandez-Hernando, Carlos; Di Lorenzo, Annarita; Sessa, William C.; Giordano, Frank J.
Arteriosclerosis, Thrombosis & Vascular Biology.
36(3):442-445, March 2016.
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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.