| Title | Smooth Muscle Hypoxia-Inducible Factor 1α Links Intravascular Pressure and Atherosclerosis--Brief Report. |
| Publication Type | Journal Article |
| Year of Publication | 2016 |
| Authors | Liu, D, Lei, L, Desir, M, Huang, Y, Cleman, J, Jiang, W, Fernandez-Hernando, C, Di Lorenzo, A, Sessa, WC, Giordano, FJ |
| Journal | Arterioscler Thromb Vasc Biol |
| Volume | 36 |
| Issue | 3 |
| Pagination | 442-5 |
| Date Published | 2016 Mar |
| ISSN | 1524-4636 |
| Keywords | Animals, Aorta, Aortic Diseases, Apolipoproteins E, Arterial Pressure, Atherosclerosis, Blood Flow Velocity, Diet, High-Fat, Disease Models, Animal, Gene Expression Regulation, Hypoxia-Inducible Factor 1, alpha Subunit, Ligation, Mice, Inbred C57BL, Mice, Knockout, Muscle, Smooth, Vascular, Plaque, Atherosclerotic, Regional Blood Flow, Signal Transduction, Time Factors |
| 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. |
| DOI | 10.1161/ATVBAHA.115.306861 |
| Alternate Journal | Arterioscler. Thromb. Vasc. Biol. |
| PubMed ID | 26800562 |
| Grant List | HL075616-02 / HL / NHLBI NIH HHS / United States HL64001 / HL / NHLBI NIH HHS / United States |