title: Hypoxia-Inducible Factor-1α in Smooth Muscle Cells Protects Against Aortic Aneurysms-Brief Report.
abstract: The purpose of this study was to determine the role of smooth muscle cell-derived hypoxia-inducible factor-1α (Hif-1α) in the pathogenesis of aortic aneurysms.
  
  
  
  Control mice and smooth muscle cell-specific hypoxia-inducible factor-1α-deficient mice were infused with β-aminopropionitrile for 2 weeks and angiotensin II for 6 weeks to induce aortic aneurysm formation. Mutant mice experienced increased levels of aneurysm formation of the thoracic or abdominal aorta with more severe elastin disruption, compared with control mice. Smooth muscle cell-specific hypoxia-inducible factor-1α deficiency did not affect matrix metalloproteinase-2 activity; however, the activity of lysyl oxidase and the levels of tropoelastin mRNA in the angiotensin II- and β-aminopropionitrile-treated aortae, associated with elastin fiber formation, were suppressed. Furthermore, we observed reduced volumes of mature cross-linked elastin in the thoracoabdominal aorta after treatment with angiotensin II and β-aminopropionitrile.
  
  
  
  Deficiency of smooth muscle cell-derived hypoxia-inducible factor-1α augments aortic aneurysms, accompanied by disruption of elastin fiber formation, but not changes of elastin fiber degradation.
authors: From the Division of Molecular Pharmacology, Faculty of Medicine, Tottori University, Japan (M.I., S.M., S.T.); Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, Japan (Y.C., M.U.); Division of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University, Japan (N.T., K.Y.); Life Science Research Center, Kagawa University, Japan (T.N.); Department of Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School, Japan (T.T.); and Department of Pharmacology, Faculty of Medicine, Osaka City University, Japan (S.T.).
authors: Masaki
authors: M
authors: Imanishi
authors: From the Division of Molecular Pharmacology, Faculty of Medicine, Tottori University, Japan (M.I., S.M., S.T.); Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, Japan (Y.C., M.U.); Division of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University, Japan (N.T., K.Y.); Life Science Research Center, Kagawa University, Japan (T.N.); Department of Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School, Japan (T.T.); and Department of Pharmacology, Faculty of Medicine, Osaka City University, Japan (S.T.).
authors: Yoichi
authors: Y
authors: Chiba
authors: From the Division of Molecular Pharmacology, Faculty of Medicine, Tottori University, Japan (M.I., S.M., S.T.); Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, Japan (Y.C., M.U.); Division of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University, Japan (N.T., K.Y.); Life Science Research Center, Kagawa University, Japan (T.N.); Department of Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School, Japan (T.T.); and Department of Pharmacology, Faculty of Medicine, Osaka City University, Japan (S.T.).
authors: Noriko
authors: N
authors: Tomita
authors: From the Division of Molecular Pharmacology, Faculty of Medicine, Tottori University, Japan (M.I., S.M., S.T.); Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, Japan (Y.C., M.U.); Division of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University, Japan (N.T., K.Y.); Life Science Research Center, Kagawa University, Japan (T.N.); Department of Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School, Japan (T.T.); and Department of Pharmacology, Faculty of Medicine, Osaka City University, Japan (S.T.).
authors: Shinji
authors: S
authors: Matsunaga
authors: From the Division of Molecular Pharmacology, Faculty of Medicine, Tottori University, Japan (M.I., S.M., S.T.); Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, Japan (Y.C., M.U.); Division of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University, Japan (N.T., K.Y.); Life Science Research Center, Kagawa University, Japan (T.N.); Department of Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School, Japan (T.T.); and Department of Pharmacology, Faculty of Medicine, Osaka City University, Japan (S.T.).
authors: Toshitaka
authors: T
authors: Nakagawa
authors: From the Division of Molecular Pharmacology, Faculty of Medicine, Tottori University, Japan (M.I., S.M., S.T.); Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, Japan (Y.C., M.U.); Division of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University, Japan (N.T., K.Y.); Life Science Research Center, Kagawa University, Japan (T.N.); Department of Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School, Japan (T.T.); and Department of Pharmacology, Faculty of Medicine, Osaka City University, Japan (S.T.).
authors: Masaki
authors: M
authors: Ueno
authors: From the Division of Molecular Pharmacology, Faculty of Medicine, Tottori University, Japan (M.I., S.M., S.T.); Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, Japan (Y.C., M.U.); Division of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University, Japan (N.T., K.Y.); Life Science Research Center, Kagawa University, Japan (T.N.); Department of Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School, Japan (T.T.); and Department of Pharmacology, Faculty of Medicine, Osaka City University, Japan (S.T.).
authors: Kazuhiro
authors: K
authors: Yamamoto
authors: From the Division of Molecular Pharmacology, Faculty of Medicine, Tottori University, Japan (M.I., S.M., S.T.); Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, Japan (Y.C., M.U.); Division of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University, Japan (N.T., K.Y.); Life Science Research Center, Kagawa University, Japan (T.N.); Department of Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School, Japan (T.T.); and Department of Pharmacology, Faculty of Medicine, Osaka City University, Japan (S.T.).
authors: Toshiaki
authors: T
authors: Tamaki
authors: From the Division of Molecular Pharmacology, Faculty of Medicine, Tottori University, Japan (M.I., S.M., S.T.); Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, Japan (Y.C., M.U.); Division of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University, Japan (N.T., K.Y.); Life Science Research Center, Kagawa University, Japan (T.N.); Department of Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School, Japan (T.T.); and Department of Pharmacology, Faculty of Medicine, Osaka City University, Japan (S.T.). tomita.shuhei@med.osaka-cu.ac.jp.
authors: Shuhei
authors: S
authors: Tomita
mesh_terms: D000629:Aminopropionitrile; D000804:Angiotensin II; D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D017545:Aortic Aneurysm, Thoracic / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002478:Cells, Cultured; D004108:Dilatation, Pathologic; D004195:Disease Models, Animal; D004547:Elastic Tissue / Q000378:metabolism / Q000473:pathology; D020022:Genetic Predisposition to Disease; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008297:Male; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D008249:Protein-Lysine 6-Oxidase / Q000378:metabolism; D014333:Tropoelastin / Q000235:genetics / Q000378:metabolism; D066253:Vascular Remodeling
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014333:Tropoelastin; D000804:Angiotensin II; D000629:Aminopropionitrile; D008249:Protein-Lysine 6-Oxidase
keywords: aneurysm; angiotensin II; elastin; extracellular matrix; hypoxia; smooth muscle; vascular remodeling