title: Role of hypoxia-inducible factor 1alpha in T cells as a negative regulator in development of vascular remodeling.
abstract: OBJECTIVE
  Recent studies have shown that the cellular immune response in the development of vascular remodeling modulates the resulting pathological alterations. We show that hypoxia-inducible factor 1 (Hif-1) (specifically expressed in T cells) is involved in the immune response to vascular remodeling that accompanies arteriosclerosis.
  
  
  RESULTS
  To study the role of T cells in the development of vascular remodeling, femoral arterial injury induced by an external vascular polyethylene cuff was examined in mice lacking Hif-1 (specifically in T cells). We found that cuff placement caused prominent neointimal hyperplasia of the femoral artery in Hif-1- (T-cell)-deficient mice compared with that in control mice and that infiltration of inflammatory cells at the adventitia was markedly increased in the mutant mice. Studies to clarify the mechanism of augmented vascular remodeling in the mutant mice showed enhanced production of cytokines by activated T cells and augmented antibody production in response to a T-dependent antigen in the mutant mice.
  
  
  CONCLUSIONS
  The results of this study revealed that Hif-1alpha in T cells plays a crucial role in vascular inflammation and remodeling in response to cuff injury as a negative regulator of T cell-mediated immune response. Potential new therapeutic strategies that target Hif-1alpha are described.
authors.affiliation: epartment of Cardiovascular Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Kurobe
authors.forename: Masahisa
authors.initials: M
authors.lastname: Urata
authors.forename: Masaki
authors.initials: M
authors.lastname: Ueno
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ueki
authors.forename: Shiro
authors.initials: S
authors.lastname: Ono
authors.forename: Yuki
authors.initials: Y
authors.lastname: Izawa-Ishizawa
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Fukuhara
authors.forename: Yu
authors.initials: Y
authors.lastname: Lei
authors.forename: Adiratna Mat
authors.initials: AM
authors.lastname: Ripen
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Kanbara
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Aihara
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ishizawa
authors.forename: Masashi
authors.initials: M
authors.lastname: Akaike
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Gonzalez
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tamaki
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Takahama
authors.forename: Masanori
authors.initials: M
authors.lastname: Yoshizumi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kitagawa
authors.forename: Shuhei
authors.initials: S
authors.lastname: Tomita
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001161:Arteriosclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015687:Cell Hypoxia; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000276:immunology / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D006965:Hyperplasia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007111:Immunity, Cellular; D007150:Immunohistochemistry; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009593:Nitroimidazoles / Q000008:administration & dosage; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000276:immunology; D013997:Time Factors; D017539:Tunica Intima / Q000276:immunology / Q000293:injuries / Q000378:metabolism* / Q000473:pathology
chemical_list: D054377:Chemokine CXCL12; D016207:Cytokines; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009593:Nitroimidazoles; D011948:Receptors, Antigen, T-Cell; C033815:pimonidazole