PMID- 30443886 OWN - NLM STAT- MEDLINE DCOM- 20200330 LR - 20200330 IS - 1868-601X (Electronic) IS - 1868-4483 (Linking) VI - 10 IP - 5 DP - 2019 Oct TI - Soluble Epoxide Hydrolase-Derived Linoleic Acid Oxylipins in Serum Are Associated with Periventricular White Matter Hyperintensities and Vascular Cognitive Impairment. PG - 522-533 LID - 10.1007/s12975-018-0672-5 [doi] AB - White matter hyperintensities (WMH) are presumed to indicate subcortical ischemic vascular disease but their underlying pathobiology remains incompletely understood. The soluble epoxide hydrolase (sEH) enzyme converts anti-inflammatory and vasoactive cytochrome p450-derived polyunsaturated fatty acid epoxides into their less active corresponding diol species. Under the hypothesis that the activity of sEH might be associated with subcortical ischemic vascular disease and vascular cognitive impairment, this study aimed to compare the relative abundance of sEH substrates and products in peripheral blood between patients with extensive WMH (discovered due to transient ischemic attack; n = 29) and healthy elderly with minimal WMH (n = 25). The concentration of 12,13-DiHOME (a sEH-derived linoleic acid metabolite), and the ratio of 12,13-DiHOME to its sEH substrate, 12,13-EpOME, were elevated in the extensive WMH group (F(1,53) = 5.9, p = 0.019), as was the 9,10-DiHOME/9,10-EpOME ratio (F(1,53) = 5.4, p = 0.024). The 12,13-DiHOME/12,13-EpOME ratio was associated with poorer performance on a composite score derived from tests of psychomotor processing speed, attention, and executive function (beta = - 0.473, p = 0.001, adjusted r(2) = 0.213), but not with a composite verbal memory score. In a mediation model, periventricular WMH (but not deep WMH), explained 37% of the effect of the 12,13-DiHOME/12,13-EpOME ratio on the speed/attention/executive function composite score (indirect effect = - 0.50, 95% bootstrap confidence interval [- 0.99, - 0.17] Z-score units). Serum oxylipin changes consistent with higher sEH activity were markers of vascular cognitive impairment, and this association was partly explained by injury to the periventricular subcortical white matter. FAU - Yu, Di AU - Yu D AD - Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada. AD - Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada. AD - Canadian Partnership for Stroke Recovery, Sunnybrook Research Institute, Toronto, Canada. AD - LC Campbell Cognitive Neurology Unit, Sunnybrook Research Institute, Toronto, Canada. FAU - Hennebelle, Marie AU - Hennebelle M AD - Department of Food Science and Technology, College of Agriculture and Environmental Sciences, University of California, Davis, CA, USA. FAU - Sahlas, Demetrios J AU - Sahlas DJ AD - Department of Medicine (Neurology Division), McMaster University, Hamilton, Canada. FAU - Ramirez, Joel AU - Ramirez J AD - Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada. FAU - Gao, Fuqiang AU - Gao F AD - Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada. FAU - Masellis, Mario AU - Masellis M AD - Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada. AD - Department of Medicine (Neurology Division), University of Toronto, Toronto, Canada. FAU - Cogo-Moreira, Hugo AU - Cogo-Moreira H AD - Departamento Psiquiatria, Universidade Federal de Sao Paulo, Sao Paulo, Brazil. AD - Department of Education and Psychology: Division of Methods and Evaluation, Freie Universitat Berlin, Berlin, Germany. FAU - Swartz, Richard H AU - Swartz RH AD - Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada. AD - Department of Medicine (Neurology Division), University of Toronto, Toronto, Canada. FAU - Herrmann, Nathan AU - Herrmann N AD - Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada. FAU - Chan, Pak Cheung AU - Chan PC AD - Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada. AD - Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, Toronto, Canada. FAU - Pettersen, Jacqueline A AU - Pettersen JA AD - Department of Medicine (Neurology Division) and the Northern Medical Program, University of British Columbia, Vancouver, Canada. FAU - Stuss, Donald T AU - Stuss DT AD - Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada. AD - Department of Medicine (Neurology Division), University of Toronto, Toronto, Canada. AD - Department of Psychology, University of Toronto, Toronto, Canada. FAU - Black, Sandra E AU - Black SE AD - Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada. AD - Canadian Partnership for Stroke Recovery, Sunnybrook Research Institute, Toronto, Canada. AD - LC Campbell Cognitive Neurology Unit, Sunnybrook Research Institute, Toronto, Canada. AD - Department of Medicine (Neurology Division), University of Toronto, Toronto, Canada. FAU - Taha, Ameer Y AU - Taha AY AD - Department of Food Science and Technology, College of Agriculture and Environmental Sciences, University of California, Davis, CA, USA. FAU - Swardfager, Walter AU - Swardfager W AUID- ORCID: 0000-0002-0030-8908 AD - Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada. w.swardfager@utoronto.ca. AD - Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada. w.swardfager@utoronto.ca. AD - Canadian Partnership for Stroke Recovery, Sunnybrook Research Institute, Toronto, Canada. w.swardfager@utoronto.ca. AD - LC Campbell Cognitive Neurology Unit, Sunnybrook Research Institute, Toronto, Canada. w.swardfager@utoronto.ca. AD - University Health Network Toronto Rehabilitation Institute, Toronto, Canada. w.swardfager@utoronto.ca. LA - eng GR - 125740/CIHR/Canada GR - 13129/CIHR/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181115 PL - United States TA - Transl Stroke Res JT - Translational stroke research JID - 101517297 RN - 0 (Biomarkers) RN - 0 (Oxylipins) RN - 9KJL21T0QJ (Linoleic Acid) RN - EC 3.3.2.- (Epoxide Hydrolases) SB - IM MH - Aged MH - Biomarkers/blood MH - Cerebral Ventricles/*pathology MH - Cognitive Dysfunction/*blood/complications MH - Cross-Sectional Studies MH - Epoxide Hydrolases/*blood MH - Female MH - Humans MH - Linoleic Acid/*blood MH - Male MH - Oxylipins/*blood MH - Vascular Diseases/*blood/complications MH - White Matter/*pathology OTO - NOTNLM OT - Linoleic acid OT - Oxylipins OT - Small vessel disease OT - Soluble epoxide hydrolase OT - Vascular cognitive impairment EDAT- 2018/11/18 06:00 MHDA- 2020/03/31 06:00 CRDT- 2018/11/17 06:00 PHST- 2018/05/23 00:00 [received] PHST- 2018/10/18 00:00 [accepted] PHST- 2018/10/15 00:00 [revised] PHST- 2018/11/18 06:00 [pubmed] PHST- 2020/03/31 06:00 [medline] PHST- 2018/11/17 06:00 [entrez] AID - 10.1007/s12975-018-0672-5 [pii] AID - 10.1007/s12975-018-0672-5 [doi] PST - ppublish SO - Transl Stroke Res. 2019 Oct;10(5):522-533. doi: 10.1007/s12975-018-0672-5. Epub 2018 Nov 15.