Soluble Epoxide Hydrolase Derived Linoleic Acid Oxylipins, Small Vessel Disease Markers, and Neurodegeneration in Stroke
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Published:2023-01-03
Issue:1
Volume:12
Page:
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ISSN:2047-9980
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Container-title:Journal of the American Heart Association
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language:en
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Short-container-title:JAHA
Author:
Yu Di12ORCID, Liang Nuanyi3ORCID, Zebarth Julia12ORCID, Shen Qing3ORCID, Ozzoude Miracle1, Goubran Maged145ORCID, Rabin Jennifer S.1467ORCID, Ramirez Joel1ORCID, Scott Christopher J. M.1ORCID, Gao Fuqiang1, Bartha Robert89, Symons Sean1, Haddad Seyyed Mohammad Hassan9ORCID, Berezuk Courtney1, Tan Brian10ORCID, Kwan Donna11, Hegele Robert A.12ORCID, Dilliott Allison A.13, Nanayakkara Nuwan D.12ORCID, Binns Malcolm A.1014ORCID, Beaton Derek10, Arnott Stephen R.10ORCID, Lawrence‐Dewar Jane M.15ORCID, Hassan Ayman15, Dowlatshahi Dar16ORCID, Mandzia Jennifer17ORCID, Sahlas Demetrios18, Casaubon Leanne19ORCID, Saposnik Gustavo20ORCID, Otoki Yurika21ORCID, Lanctôt Krista L.122223ORCID, Masellis Mario1624, Black Sandra E.1624ORCID, Swartz Richard H.1624, Taha Ameer Y.3ORCID, Swardfager Walter1225ORCID, Rashkovan Natalie, Black Sandra E., Abrahao Agessandro, Zinman Lorne, Bonnick Alisia, Swartz Richard H., Masellis Mario, Ramirez Joel, Scott Christopher, Symons Sean, Berezuk Courtney, Holmes Melissa, Adamo Sabrina, Ozzoude Miracle, Freedman Morris, Tan Brian, Zamyadi Mojdeh, Arnott Stephen, Beaton Derek, Binns Malcolm, Raamana Pradeep, Strother Stephen, Sunderland Kelly, Theyers Athena, Uthirakumaran Abiramy, Levine Brian, Troyer Angela, Strong Michael, Kleinstiver Peter, Borrie Michael, Finger Elizabeth, Shoesmith Christen, Faria Frederico, Montero‐Odasso Manuel, Sarquis‐Adamson Yanina, Black Alanna, Mandzia Jennifer, Dilliott Allison Ann, Hegele Rob, Robinson John, Farhan Sali, Bartha Rob, Haddad Hassan, Nanayakkara Nuwan, Zou Guangyong, Pasternak Stephen, Orange JB, Roberts Angela, Jog Mandar, Seitz Dallas, Brien Don, Chen Ying, Coe Brian, Munoz Doug, McLaughlin Paula, Peltsch Alicia, Kwan Donna, Bronskill Susan, Lou Wendy, Kumar Sanjeev, Pollock Bruce, Rajji Tarek, Tang‐Wai David, Tartaglia Carmela, Varriano Brenda, Chum Marvin, Turnbull John, Lawrence‐Dewar Jane, Hassan Ayman, Fraser Julia, McIlroy Bill, Cornish Ben, Van Ooteghem Karen, Hudson Chris, Leontieva Elena, Hatch Wendy, Tayyari Faryan, Defrawy Sherif, Margolin Edward, Mandelcorn Efrem, Greenberg Barry, Casaubon Leanne, Lang Anthony, Marras Connie, Frank Andrew, Dowlatshahi Dar, Grimes David, Bulman Dennis, Woulfe John, Ghani Mahdi, Sahlas Demetrios, Saposnik Gustavo, Steeves Tom, Munoz David, Fischer Corinne, Rogaeva Ekaterina, Sujanthan Sujeevini, Breen David, Dixon Roger A.
Affiliation:
1. Dr. Sandra Black Center for Brain Resilience & Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute Toronto Canada 2. Department of Pharmacology and Toxicology University of Toronto Toronto Canada 3. Department of Food Science and Technology University of California Davis CA 4. Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre Toronto Canada 5. Department of Medical Biophysics University of Toronto Toronto Canada 6. Division of Neurology, Department of Medicine Sunnybrook Health Sciences Centre Toronto Canada 7. Rehabilitation Sciences Institute University of Toronto Toronto Canada 8. Department of Medical Biophysics Western University London Canada 9. Center for Functional and Metabolic Mapping, Robarts Research Institute Western University London Canada 10. Rotman Research Institute, Baycrest Health Sciences Centre Toronto Canada 11. Centre for Neuroscience Studies Queen’s University Kingston Canada 12. Robarts Research Institute Western University London Canada 13. Department of Neurology and Neurosurgery McGill University Montreal Canada 14. Dalla Lana School of Public Health University of Toronto Toronto Canada 15. Thunder Bay Regional Health Research Institute Northern Ontario School of Medicine University Thunder Bay Canada 16. Department of Medicine (Neurology), Ottawa Hospital Research Institute University of Ottawa Ottawa Canada 17. Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry Western University London Canada 18. Division of Neurology, Department of Medicine, Faculty of Health Sciences McMaster University Hamilton Canada 19. Krembil Research Institute University Health Network Toronto Canada 20. Stroke Outcomes and Decision Neuroscience Research Unit, Division of Neurology, St. Michael’s Hospital University of Toronto Toronto Canada 21. Division of Agricultural Chemistry, Graduate School of Agricultural Science Tohoku University Sendai Japan 22. Department of Psychiatry, Faculty of Medicine University of Toronto Toronto Canada 23. Hurvitz Brain Sciences Program, Sunnybrook Research Institute Toronto Canada 24. Department of Neurology, Faculty of Medicine University of Toronto Toronto Canada 25. Toronto Rehabilitation Institute University Health Network Toronto Canada
Abstract
Background
Cerebral small vessel disease is associated with higher ratios of soluble‐epoxide hydrolase derived linoleic acid diols (12,13‐dihydroxyoctadecenoic acid [DiHOME] and 9,10‐DiHOME) to their parent epoxides (12(13)‐epoxyoctadecenoic acid [EpOME] and 9(10)‐EpOME); however, the relationship has not yet been examined in stroke.
Methods and Results
Participants with mild to moderate small vessel stroke or large vessel stroke were selected based on clinical and imaging criteria. Metabolites were quantified by ultra‐high‐performance liquid chromatography–mass spectrometry. Volumes of stroke, lacunes, white matter hyperintensities, magnetic resonance imaging visible perivascular spaces, and free water diffusion were quantified from structural and diffusion magnetic resonance imaging (3 Tesla). Adjusted linear regression models were used for analysis. Compared with participants with large vessel stroke (n=30), participants with small vessel stroke (n=50) had a higher 12,13‐DiHOME/12(13)‐EpOME ratio (β=0.251,
P
=0.023). The 12,13‐DiHOME/12(13)‐EpOME ratio was associated with more lacunes (β=0.266,
P
=0.028) but not with large vessel stroke volumes. Ratios of 12,13‐DiHOME/12(13)‐EpOME and 9,10‐DiHOME/9(10)‐EpOME were associated with greater volumes of white matter hyperintensities (β=0.364,
P
<0.001; β=0.362,
P
<0.001) and white matter MRI‐visible perivascular spaces (β=0.302,
P
=0.011; β=0.314,
P
=0.006). In small vessel stroke, the 12,13‐DiHOME/12(13)‐EpOME ratio was associated with higher white matter free water diffusion (β=0.439,
P
=0.016), which was specific to the temporal lobe in exploratory regional analyses. The 9,10‐DiHOME/9(10)‐EpOME ratio was associated with temporal lobe atrophy (β=−0.277,
P
=0.031).
Conclusions
Linoleic acid markers of cytochrome P450/soluble‐epoxide hydrolase activity were associated with small versus large vessel stroke, with small vessel disease markers consistent with blood brain barrier and neurovascular‐glial disruption, and temporal lobe atrophy. The findings may indicate a novel modifiable risk factor for small vessel disease and related neurodegeneration.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine
Cited by
4 articles.
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