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      Hypoxia, oxidative stress and inflammation.

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          Abstract

          Inflammatory Arthritis is characterized by synovial proliferation, neovascularization and leukocyte extravasation leading to joint destruction and functional disability. Efficiency of oxygen supply to the synovium is poor due to the highly dysregulated synovial microvasculature. This along with the increased energy demands of activated infiltrating immune cells and inflamed resident cells leads to an hypoxic microenvironment and mitochondrial dysfunction. This favors an increase of reactive oxygen species, leading to oxidative damage which further promotes inflammation. In this adverse microenvironment synovial cells adapt to generate energy and switch their cell metabolism from a resting regulatory state to a highly metabolically active state which allows them to produce essential building blocks to support their proliferation. This metabolic shift results in the accumulation of metabolic intermediates which act as signaling molecules that further dictate the inflammatory response. Understanding the complex interplay between hypoxia-induced signaling pathways, oxidative stress and mitochondrial function will provide better insight into the underlying mechanisms of disease pathogenesis.

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          Author and article information

          Journal
          Free Radic Biol Med
          Free radical biology & medicine
          Elsevier BV
          1873-4596
          0891-5849
          September 2018
          : 125
          Affiliations
          [1 ] The Department of Molecular Rheumatology, Trinity College Dublin, Ireland.
          [2 ] The Centre for Arthritis and Rheumatic Disease, Dublin Academic Medical Centre, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
          [3 ] The Department of Molecular Rheumatology, Trinity College Dublin, Ireland. Electronic address: fearonu@tcd.ie.
          Article
          S0891-5849(18)30145-X
          10.1016/j.freeradbiomed.2018.03.042
          29601945
          5394712c-ca96-405a-8ca3-8fb0f9bf41dc
          History

          Altered cellular metabolism,Dysregulated angiogenesis,Hypoxia,Inflammatory arthritis,Mitochondrial dysfunction,Oxidative stress

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