Role of Hypoxia-Inducible Factor 1α in T Cells as a Negative Regulator in Development of Vascular Remodeling
Open accessAbstract
Background and Purpose— 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. Methods and 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-1α 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-1α are described.
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T cell-specific Hif-1α KO mice have increased inflammatory cell infiltration and vascular remodeling in a vascular injury model.
“T cell-specific Hif-1α KO mice also had increased inflammatory cell infiltration and vascular remodeling in a vascular injury model [94].”
From Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function (2013) · cites this paper as [94]
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- Authors
- Kurobe, H., Urata, M., Ueno, M., Ueki, M., Ono, S., Izawa-Ishizawa, Y., Fukuhara, Y., Lei, Y., Ripen, A. M., Kanbara, T., Aihara, K.-I., Ishizawa, K., Akaike, M., Gonzalez, F. J., Tamaki, T., Takahama, Y., Yoshizumi, M., Kitagawa, T., & Tomita, S.
- Affiliations
- National Institutes of Health (US)
- From the Department of Cardiovascular Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan (H.K., M.U., T.K., and T.K.); the Department of Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan (Y.I.-I., Y.F., K.I., T.T., and S.T.); the Division of Experimental Immunology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan (Y.L., A.M.R., Y.T., and S.T....
- ORCID
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2010-02
- Volume
- 30
- Issue
- 2
- Pages
- 210-217
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- PMC
- PMC6392182
- OpenAlex
- W2048316334
- Cited by
- 35
- References
- 28
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 3 · 2014: 1 · 2013: 2 · 2012: 3
- FWCI
- 1.29
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Japan Society for the Promotion of Science (21590335)
- National Cancer Institute (Z01BC005561)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
- Keywords
- hypoxia-inducible factor-1α, T cells, vascular remodeling, arteriosclerosis, intimal hyperplasia, vascular inflammation, T cell immunity, cytokine production, antibody production
- MeSH terms
- Animals, Antibody Formation, Arteriosclerosis, Chemotaxis, Leukocyte, Disease Models, Animal, Femoral Artery, Hyperplasia, Immunity, Cellular, Immunohistochemistry, Lymphocyte Activation, Male, Nitroimidazoles, Receptors, Antigen, T-Cell, T-Lymphocytes, Thymus Gland, Time Factors, Cell Hypoxia, Cytokines, Tunica Intima, Mice, Knockout, Cell Proliferation, Mice, Hypoxia-Inducible Factor 1, alpha Subunit, Chemokine CXCL12
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