1. Smooth Muscle Hypoxia-Inducible Factor 1α Links Intravascular Pressure and Atherosclerosis--Brief Report.
- Author
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Liu D, Lei L, Desir M, Huang Y, Cleman J, Jiang W, Fernandez-Hernando C, Di Lorenzo A, Sessa WC, and Giordano FJ
- Subjects
- Animals, Aorta metabolism, Aorta physiopathology, Aortic Diseases genetics, Aortic Diseases pathology, Aortic Diseases physiopathology, Aortic Diseases prevention & control, Apolipoproteins E deficiency, Apolipoproteins E genetics, Atherosclerosis genetics, Atherosclerosis pathology, Atherosclerosis physiopathology, Atherosclerosis prevention & control, Blood Flow Velocity, Diet, High-Fat, Disease Models, Animal, Gene Expression Regulation, Hypoxia-Inducible Factor 1, alpha Subunit deficiency, Hypoxia-Inducible Factor 1, alpha Subunit genetics, Ligation, Mice, Inbred C57BL, Mice, Knockout, Muscle, Smooth, Vascular pathology, Muscle, Smooth, Vascular physiopathology, Muscle, Smooth, Vascular surgery, Plaque, Atherosclerotic, Regional Blood Flow, Signal Transduction, Time Factors, Aortic Diseases metabolism, Arterial Pressure, Atherosclerosis metabolism, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Muscle, Smooth, Vascular metabolism
- 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., (© 2016 American Heart Association, Inc.)
- Published
- 2016
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