TY - JOUR
T1 - Soluble Epoxide Hydrolase Derived Linoleic Acid Oxylipins, Small Vessel Disease Markers, and Neurodegeneration in Stroke
AU - ONDRI Investigators [Link]
AU - Yu, Di
AU - Liang, Nuanyi
AU - Zebarth, Julia
AU - Shen, Qing
AU - Ozzoude, Miracle
AU - Goubran, Maged
AU - Rabin, Jennifer S.
AU - Ramirez, Joel
AU - Scott, Christopher J.M.
AU - Gao, Fuqiang
AU - Bartha, Robert
AU - Symons, Sean
AU - Haddad, Seyyed Mohammad Hassan
AU - Berezuk, Courtney
AU - Tan, Brian
AU - Kwan, Donna
AU - Hegele, Robert A.
AU - Dilliott, Allison A.
AU - Nanayakkara, Nuwan D.
AU - Binns, Malcolm A.
AU - Beaton, Derek
AU - Arnott, Stephen R.
AU - Lawrence-Dewar, Jane M.
AU - Hassan, Ayman
AU - Dowlatshahi, Dar
AU - Mandzia, Jennifer
AU - Sahlas, Demetrios
AU - Casaubon, Leanne
AU - Saposnik, Gustavo
AU - Otoki, Yurika
AU - Lanctôt, Krista L.
AU - Masellis, Mario
AU - Black, Sandra E.
AU - Swartz, Richard H.
AU - Taha, Ameer Y.
AU - Swardfager, Walter
PY - 2023/1/3
Y1 - 2023/1/3
N2 - 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.
AB - 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.
KW - lacunar stroke
KW - oxylipin
KW - small vessel disease
KW - soluble epoxide hydrolase
KW - white matter hyperintensity
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U2 - 10.1161/JAHA.122.026901
DO - 10.1161/JAHA.122.026901
M3 - Article
C2 - 36583428
AN - SCOPUS:85145492041
SN - 2047-9980
VL - 12
SP - e026901
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 1
ER -