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First, we compared molecular markers of hypoxia\u2010inducible factor (HIF) pathway activation (<jats:italic>BNIP3<\/jats:italic>, <jats:italic>GLUT1<\/jats:italic>, <jats:italic>HO1, VEGF,<\/jats:italic> and <jats:italic>HIF1A<\/jats:italic>) and inflammatory response (<jats:italic>IL1B<\/jats:italic> and <jats:italic>COX2<\/jats:italic>) in tissue from patients undergoing revision of MoM hip implant with tissue from patients undergoing primary hip replacement (PHR). Second, we compared blood levels of the above molecular markers and additional inflammatory markers: <jats:italic>TNFA<\/jats:italic>, <jats:italic>IL18<\/jats:italic>, <jats:italic>CASPASE1<\/jats:italic>, <jats:italic>NFKB<\/jats:italic> or <jats:italic>IKB<\/jats:italic>, and <jats:italic>TLR1\u20134<\/jats:italic> mRNA in patients with non\u2010failed MoM hips. We report the presence of increased expression of HIF\u2010target genes in the periprosthetic tissue in MoM patients when compared to the PHR group. This suggests HIF pathway activation due to MoM debris and the potential of using HIF targets as a predictor of failure. Analysis of blood samples from nonoverlapping, nonfailed, MoM group showed significantly higher expression of <jats:italic>COX2<\/jats:italic> mRNA and significant correlations between <jats:italic>HIF1A<\/jats:italic> and <jats:italic>GLUT1<\/jats:italic> mRNA expressions, and between <jats:italic>HIF1A<\/jats:italic> mRNA and selection of inflammatory genes, including <jats:italic>IL18<\/jats:italic>, <jats:italic>IKB<\/jats:italic>, <jats:italic>TLR1<\/jats:italic>, and <jats:italic>TLR4<\/jats:italic>. HIF pathway activation in the periprosthetic tissue biopsies of patients with hip replacements may represent the first biomarker to identify early ARMD. Further studies investigating blood biomarkers could also prove beneficial in detecting ARMD that could lead to an early intervention and improved patient outcome after hip revision surgery. \u00a9 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1352\u20131362, 2019.<\/jats:p>","DOI":"10.1002\/jbm.b.34227","type":"journal-article","created":{"date-parts":[[2018,9,27]],"date-time":"2018-09-27T18:59:50Z","timestamp":1538074790000},"page":"1352-1362","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Molecular analysis of HIF activation as a potential biomarker for adverse reaction to metal debris (ARMD) in tissue and blood samples"],"prefix":"10.1002","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3561-5518","authenticated-orcid":false,"given":"Agata","family":"Nyga","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, National Heart &amp; Lung Institute, Imperial College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alister","family":"Hart","sequence":"additional","affiliation":[{"name":"Institute of Orthopaedics &amp; Musculoskeletal Science Royal National Orthopaedic Hospital, University College London  Stanmore UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa D.","family":"Tetley","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, National Heart &amp; 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