Linoleic Acid Metabolite DiHOME Decreases Post-ischemic Cardiac Recovery in Murine Hearts.
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.
['Bannehr|Marwin|M|0000-0001-9762-4167', 'Löhr|Lena|L|', 'Gelep|Julia|J|', 'Haverkamp|Wilhelm|W|', 'Schunck|Wolf-Hagen|WH|', 'Gollasch|Maik|M|', 'Wutzler|Alexander|A|']
D000218:Adamantane D000818:Animals D004195:Disease Models, Animal D004791:Enzyme Inhibitors D004851:Epoxide Hydrolases D000067268:Isolated Heart Preparation D007850:Lauric Acids D019787:Linoleic Acid D008297:Male D008810:Mice, Inbred C57BL D015428:Myocardial Reperfusion Injury D009206:Myocardium D009829:Oleic Acids D020127:Recovery of Function D015398:Signal Transduction D016277:Ventricular Function, Left D017725:Ventricular Pressure
Linoleic acid Ischemia/reperfusion injury Epoxyoctadecanoic acid (EpOME) Dihydroxyoctadecanoic acid (DiHOME) Soluble epoxide hydrolase (sEH) 12-(3-Adamantan-1-yl-ureido)dodecanoic acid (AUDA) Langendorff perfused heart