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Linoleic acid metabolite DiHOME decreases post-ischemic cardiac recovery in murine hearts

Item Type:Article
Title:Linoleic acid metabolite DiHOME decreases post-ischemic cardiac recovery in murine hearts
Creators Name:Bannehr, M. and Löhr, L. and Gelep, J. and Haverkamp, W. and Schunck, W.H. and Gollasch, M. and Wutzler, A.
Abstract:Cardiac ischemia/reperfusion injury is associated with the formation and action of lipid mediators derived from polyunsaturated fatty acids. Among them, linoleic acid (LA) is metabolized to epoxyoctadecanoic acids (EpOMEs) by cytochrome P450 (CYP) epoxygenases and further to dihydroxyoctadecanoic acids (DiHOMEs) by soluble epoxide hydrolase (sEH). We hypothesized that EpOMEs and/or DiHOMEs may affect cardiac post-ischemic recovery and addressed this question using isolated murine hearts in a Langendorff system. Hearts from C57Bl6 mice were exposed to 12,13-EpOME, 12,13-DiHOME, or vehicle (phosphate buffered sodium; PBS). Effects on basal cardiac function and functional recovery during reperfusion following 20 min of ischemia were investigated. Electrocardiogram (ECG), left ventricular (LV) pressure and coronary flow (CF) were continuously measured. Ischemia reperfusion experiments were repeated after administration of the sEH-inhibitor 12-(3-adamantan-1-yl-ureido)dodecanoic acid (AUDA). At a concentration of 100 nM, both EpOME and DiHOME decreased post-ischemic functional recovery in murine hearts. There was no effect on basal cardiac parameters. The detrimental effects seen with EpOME, but not DiHOME, were averted by sEH inhibition (AUDA). Our results indicate that LA-derived mediators EpOME/DiHOME may play an important role in cardiac ischemic events. Inhibition of sEH could provide a novel treatment option to prevent detrimental DiHOME effects in acute cardiac ischemia.
Keywords:Epoxyoctadecanoic Acid (EpOME), Dihydroxyoctadecanoic Acid (DiHOME), Soluble Epoxide Hydrolase (sEH), Linoleic Acid, Langendorff Perfused Heart, Ischemia/Reperfusion Injury, 12-(3-Adamantan-1-yl-Ureido) Dodecanoic Acid (AUDA), Animals, Mice
Source:Cardiovascular Toxicology
Publisher:Springer / Humana Press
Page Range:365-371
Date:August 2019
Official Publication:https://doi.org/10.1007/s12012-019-09508-x
PubMed:View item in PubMed

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