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Linoleic Acid Metabolite DiHOME Decreases Post-ischemic Cardiac Recovery in Murine Hearts

  • Marwin BannehrEmail author
  • Lena Löhr
  • Julia Gelep
  • Wilhelm Haverkamp
  • Wolf-Hagen Schunck
  • Maik Gollasch
  • Alexander Wutzler
Article
  • 16 Downloads

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) 

Abbreviations

AUDA

12-(3-Adamantan-1-yl-ureido)dodecanoic acid

CF

Coronary flow

CYP

Cytochrome P450

DiHOME

Dihydroxyoctadecanoic acid

EET

Epoxyeicosatrienoic acid

EpOME

Epoxyoctadecanoic acid

HR

Heart rate

LA

Linoleic acid

LV

Left ventricle

LVdia

Left ventricular diastolic pressure

LVDP

Left ventricular developed pressure

PBS

Phosphate-buffered sodium

sEH

Soluble epoxide hydrolase

Notes

Acknowledgements

In this work results of the dissertation “Effekte der Linolsäurederivate 12,13-Epoxyoctadecensäure(-methylester) und 12,13-Dihydroxyoctadecensäure(-methylester) auf das isolierte murine Herz” by Marwin Bannehr submitted in 2019 to Charité - Universitätsmedizin Berlin have been included. The authors thank Bastian Spallek, Michael Gotthardt and Ingo Morano for technical support and assistance during the experiments.

Compliance with Ethical Standards

Disclosure

All authors have nothing to disclose.

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Authors and Affiliations

  1. 1.Department of CardiologyCharité - Universitätsmedizin BerlinBerlinGermany
  2. 2.Max-Delbrück-Center for Molecular MedicineBerlinGermany
  3. 3.Experimental and Clinical Research CenterBerlinGermany
  4. 4.Department of Nephrology and Intensive Care MedicineCharité - Universitätsmedizin BerlinBerlinGermany
  5. 5.Department of Electrophysiology and Cardiac Rhythm Management, St. Joseph HospitalRuhr-University BochumBochumGermany

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