Pathophysiological Response to Hypoxia - From the Molecular Mechanisms of Malady to Drug Discovery:Inflammatory Responses of Hypoxia-Inducible Factor 1.ALPHA. (HIF-1.ALPHA.) in T Cells Observed in Development of Vascular Remodeling

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  • Tomita Shuhei
    Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan
  • Kihira Yoshitaka
    Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan
  • Imanishi Masaki
    Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan
  • Fukuhara Yayoi
    Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan
  • Imamura Yuko
    Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan
  • Ishizawa Keisuke
    Department of Medical Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan
  • Ikeda Yasumasa
    Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan
  • Tsuchiya Koichiro
    Department of Medical Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan
  • Tamaki Toshiaki
    Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan

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Other Title
  • Inflammatory responses of hypoxia-inducible factor 1α (HIF-1α) in T cells observed in development of vascular remodeling
  • Inflammatory responses of hypoxia inducible factor 1 a HIF 1 a in T cells observed in development of vascular remodeling
  • Pathophysiological Response to Hypoxia — From the Molecular Mechanisms of Malady to Drug Discovery: Inflammatory Responses of Hypoxia-Inducible Factor 1α (HIF-1α) in T Cells Observed in Development of Vascular Remodeling

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Abstract

Recent studies have shown that the cellular immune response to the hypoxic microenvironment constructed by vascular remodeling development modulates the resulting pathologic alterations. A major mechanism mediating adaptive responses to reduced oxygen availability is the regulation of transcription by hypoxia-inducible factor 1 (HIF-1). Impairment of HIF-1–dependent inflammatory responses in T cells causes an augmented vascular remodeling induced by arterial injury, which is shown as prominent neointimal hyperplasia and increase in infiltration of inflammatory cells at the adventitia in mice lacking Hif-1α specifically in T cells. Studies to clarify the mechanism of augmented vascular remodeling in the mutant mice have shown enhanced production of cytokines in activated T cells and augmented antibody production in response to a T-dependent antigen in the mutant mice. This minireview shows that HIF-1α in T cells plays a crucial role in vascular inflammation and remodeling in response to cuff injury as a negative regulator of the T cell–mediated immune response and suggests potential new therapeutic strategies that target HIF-1α.

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