title: Role of macrophage-derived hypoxia-inducible factor (HIF)-1α as a mediator of vascular remodelling.
abstract: OBJECTIVE
  Excessive vascular remodelling leads to progression of a wide range of vasculopathies, and the immune response to intimal injuries is crucial in this process. This vascular remodelling occurs in the hypoxic microenvironment and is closely related to the immune system. Macrophages play a key role in immunological-cell-mediated arterial remodelling. In this study, we clarified the role of macrophage-derived hypoxia-inducible factor (HIF-1α) in vascular remodelling.
  
  
  RESULTS
  Wire-induced femoral arterial injury was inflicted in mice lacking the macrophage-specific HIF-1α gene and in their wild-type counterparts. The mutant mice showed both suppressed wire-induced neointimal thickening and decreased infiltration of inflammatory cells in the adventitia, compared with wild-type mice. Studies to clarify the mechanism of restrained vascular remodelling in the mutant mice revealed decreased production of pro-inflammatory cytokines by the activated macrophages and suppressed macrophage migration activity in the mutant mice. Gene expressions of the HIF-1α-deficient macrophages positively correlated with the phenotypic profile of M2 macrophages and negatively correlated with that of M1 macrophages.
  
  
  CONCLUSIONS
  Our results show that HIF-1α in macrophages plays a crucial role in promoting vascular inflammation and remodelling. As decreasing HIF-1α activity in macrophages may prevent the progression of vascular remodelling, HIF-1α may be a possible therapeutic target in vascular diseases.
authors.affiliation: Department of Cardiovascular Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Nakayama
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Kurobe
authors.forename: Noriko
authors.initials: N
authors.lastname: Sugasawa
authors.forename: Hajime
authors.initials: H
authors.lastname: Kinoshita
authors.forename: Mayuko
authors.initials: M
authors.lastname: Higashida
authors.forename: Yuki
authors.initials: Y
authors.lastname: Matsuoka
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Hirata
authors.forename: Mie
authors.initials: M
authors.lastname: Sakata
authors.forename: Mark W
authors.initials: MW
authors.lastname: Maxfield
authors.forename: Michio
authors.initials: M
authors.lastname: Shimabukuro
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Takahama
authors.forename: Masataka
authors.initials: M
authors.lastname: Sata
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tamaki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kitagawa
authors.forename: Shuhei
authors.initials: S
authors.lastname: Tomita
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000473:pathology*; D002465:Cell Movement; D024243:HMGB1 Protein / Q000502:physiology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology*; D015850:Interleukin-6 / Q000032:analysis; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha
keywords: Hypoxia-inducible factor (HIF); Macrophage; Vascular remodelling