title: 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.
  
  
  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.
authors.affiliation: From the Departments of Medicine (D.L., L.L., M.D., Y.H., J.C., W.J., F.J.G.) and Pharmacology (W.C.S.), Yale University, New Haven, CT; Department of Pathology, NYU Langone Medical Center, New York, NY (C.F.-H.); and Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY (A.D.L.).
authors.forename: Dinggang
authors.initials: D
authors.lastname: Liu
authors.affiliation: From the Departments of Medicine (D.L., L.L., M.D., Y.H., J.C., W.J., F.J.G.) and Pharmacology (W.C.S.), Yale University, New Haven, CT; Department of Pathology, NYU Langone Medical Center, New York, NY (C.F.-H.); and Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY (A.D.L.).
authors.forename: Li
authors.initials: L
authors.lastname: Lei
authors.affiliation: From the Departments of Medicine (D.L., L.L., M.D., Y.H., J.C., W.J., F.J.G.) and Pharmacology (W.C.S.), Yale University, New Haven, CT; Department of Pathology, NYU Langone Medical Center, New York, NY (C.F.-H.); and Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY (A.D.L.).
authors.forename: Matthew
authors.initials: M
authors.lastname: Desir
authors.affiliation: From the Departments of Medicine (D.L., L.L., M.D., Y.H., J.C., W.J., F.J.G.) and Pharmacology (W.C.S.), Yale University, New Haven, CT; Department of Pathology, NYU Langone Medical Center, New York, NY (C.F.-H.); and Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY (A.D.L.).
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: From the Departments of Medicine (D.L., L.L., M.D., Y.H., J.C., W.J., F.J.G.) and Pharmacology (W.C.S.), Yale University, New Haven, CT; Department of Pathology, NYU Langone Medical Center, New York, NY (C.F.-H.); and Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY (A.D.L.).
authors.forename: Jacob
authors.initials: J
authors.lastname: Cleman
authors.affiliation: From the Departments of Medicine (D.L., L.L., M.D., Y.H., J.C., W.J., F.J.G.) and Pharmacology (W.C.S.), Yale University, New Haven, CT; Department of Pathology, NYU Langone Medical Center, New York, NY (C.F.-H.); and Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY (A.D.L.).
authors.forename: Weidong
authors.initials: W
authors.lastname: Jiang
authors.affiliation: From the Departments of Medicine (D.L., L.L., M.D., Y.H., J.C., W.J., F.J.G.) and Pharmacology (W.C.S.), Yale University, New Haven, CT; Department of Pathology, NYU Langone Medical Center, New York, NY (C.F.-H.); and Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY (A.D.L.).
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernandez-Hernando
authors.affiliation: From the Departments of Medicine (D.L., L.L., M.D., Y.H., J.C., W.J., F.J.G.) and Pharmacology (W.C.S.), Yale University, New Haven, CT; Department of Pathology, NYU Langone Medical Center, New York, NY (C.F.-H.); and Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY (A.D.L.).
authors.forename: Annarita
authors.initials: A
authors.lastname: Di Lorenzo
authors.affiliation: From the Departments of Medicine (D.L., L.L., M.D., Y.H., J.C., W.J., F.J.G.) and Pharmacology (W.C.S.), Yale University, New Haven, CT; Department of Pathology, NYU Langone Medical Center, New York, NY (C.F.-H.); and Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY (A.D.L.).
authors.forename: William C
authors.initials: WC
authors.lastname: Sessa
authors.affiliation: From the Departments of Medicine (D.L., L.L., M.D., Y.H., J.C., W.J., F.J.G.) and Pharmacology (W.C.S.), Yale University, New Haven, CT; Department of Pathology, NYU Langone Medical Center, New York, NY (C.F.-H.); and Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY (A.D.L.). frank.giordano@yale.edu.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Giordano
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000503:physiopathology; D001018:Aortic Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D062186:Arterial Pressure; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D001783:Blood Flow Velocity; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008026:Ligation; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D058226:Plaque, Atherosclerotic; D012039:Regional Blood Flow; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D001057:Apolipoproteins E; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit
keywords: atherosclerosis; blood pressure; hypoxia-inducible factor; inflammation; smooth muscle