Serum oxylipins indicate subcortical ischemic vascular disease in patients with clinical stroke. (1st February 2022)

• Record Type: Journal Article
• Authors: Yu, Di; Taha, Ameer; Pedersen, Theresa; Joel, Ramirez; Goubran, Maged; Ozzoude, Miracle; Gao, Fuqiang; Casaubon, Leanne; Bartha, Robert; Symons, Sean; Kwan, Donna; Dowlatshahi, Dar; Hassan, Ayman; Mandzia, Jennifer; Sahlas, Demetrios J.; Saposnik, Gustavo; Arnott, Stephen R.; Tan, Brian; Lanctôt, Krista L.; Masellis, Mario; Black, Sandra E.; Swartz, Richard H.; Swardfager, Walter
• Is Part Of: Alzheimer's & dementia. Volume 17(2021)Supplement 4
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-01
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.050909
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Subcortical ischemic vascular disease (SIVD) is the most common vascular pathology found in patients with late onset dementia. The soluble epoxide hydrolase (sEH) enzyme inactivates anti‐inflammatory and vasoactive cytochrome p450 derived polyunsaturated fatty acid epoxides by converting them into cytotoxic dihydroxy (diol) oxylipin species. Previously, we found that the ratios of linoleic acid (LA) diols to epoxides were associated with more white matter hyperintensity (WMH) in patients with transient ischemic attack; however, it remains univestigated if these oxylipins can identify SIVD in patients with ischemic stroke of heterogenous cerebrovascular pathologies such as large vessel occlusion and lacunar infarcts. Method: The study cohort comprises patients from the Ontario Neurodegenerative Disease Research Initiative, who has clinical stroke of either large or small vessel etiology (according to TOAST criteria). 4 LA oxylipins (12, 13‐dihydroxyoctadecamonoenoic acid (12, 13‐DiHOME), 12, 13‐epoxyoctadecenoic acid (12, 13‐EpOME), 9, 10‐DiHOME, 9, 10‐EpOME) were extracted from blood and quantified with a targeted ultrahigh pressure liquid chromatography mass spectrometry (UPLC‐MS/MS) WMH and perivascular spaces (PVS) were quantified from structural MRI scans using a personalized semi‐automatic processing pipeline (Lesion Explorer). The associations between oxylipins and small vessel disease markers were examined using linear regression models. Result: In 80 stroke patients (n=50 large vessel disease and n=30 lacunar infarcts), the ratio of 12, 13‐DiHOME to its epoxide sEH substrate 12, 13‐EpOME was higher among patients with small vessel etiology (F1, 79 = 4.55, p = 0.036). In linear regression models controlling for age, sex, APOE, waist hip ratio, diabetes, and hyperlipidemia, the same ratio, and the ratio of 9, 10‐DiHOME/9, 10‐EpOME were positively associated with volume of deep (β = 0.338, p = 0.004; β = 0.288, p = 0.012, respectively) and periventricular (β = 0.316, p = 0.003; β = 0.400, p < 0.001, respectively) WMH. The same ratios were associated with higher volumes of perivascular spaces in the white matter (β = 0.293, p = 0.013; β = 0.276, p = 0.016, respectively) but not in the basal ganglia (β = 0.145, p = 0.212; β = 0.086, p = 0.450, respectively). Conclusion: Oxylipins derived from sEH activity may contribute to cerebral small vessel disease and to stroke of small vessel etiology.