Omega-6 oxylipins generated by soluble epoxide hydrolase are associated with knee osteoarthritis

Journal of Lipid Research

Srinivasarao Ravipati¹  Massimo Mangino²  Cristina Menni³  Petros Pousinis⁴  Abhishek Abhishek⁵  Victoria Chapman⁵  David A. Barrett⁶  Michael Doherty⁶  Ana M. Valdes⁷ 

[1] Academic Rheumatology, Nottingham City Hospital, Nottingham, United Kingdom;Arthritis Research UK Centre of Excellence for Pain, University of Nottingham, Nottingham, United Kingdom;Department of Twin Research, King's College London, St Thomas' Hospital, London, United Kingdom;National Institute for Health Research Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, United Kingdom;Centre for Analytical Bioscience, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom;Department of Twin Research, King's College London, St Thomas' Hospital, London, United Kingdom;To whom correspondence should be addressed.;

关键词: lipids;    arachidonic acid;    eicosanoids;    inflammation;    methods/high-performance liquid chromatography;    lipidomics;   

DOI  :  

来源: DOAJ

【 摘 要 】

Omega-6 FAs are inflammatory mediators that are increased in joints with osteoarthritis (OA), but their association with OA progression is not yet well defined. To investigate the relationship between omega-6 FAs and knee OA, we measured with LC-MS the levels of 22 omega-6 lipids (arachidonic acid, linoleic acid, and 20 oxylipins) in synovial fluid (SF) from 112 knees of 102 individuals (58 with knee OA; 44 controls). We hypothesized that oxylipin metabolites would increase in OA knee SF and with radiographically progressive disease. We validated results by comparing samples from affected and unaffected knees in 10 individuals with unilateral OA. In adjusted analysis, SF levels of three omega-6 oxylipins [prostaglandin D2, 11,12-dihydroxyeicosatrienoic acid (DHET), and 14,15-DHET] were associated with OA. Of these, 11,12-DHET and 14,15-DHET were higher in affected versus unaffected knees of people with unilateral disease (P < 0.014 and P < 0.003, respectively). Levels of these and 8,9-DHET were also associated with radiographic progression over 3.3 years in 87 individuals. Circulating levels of all three were associated with gene variants at the soluble epoxide hydrolase enzyme. Lipidomic profiling in SF identified an additional inflammatory pathway associated with knee OA and radiographic progression.

【 授权许可】

Unknown