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Cardiovascular Toxicology
Erschienen in: Cardiovascular Toxicology 4/2019

06.02.2019

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

verfasst von: Marwin Bannehr, Lena Löhr, Julia Gelep, Wilhelm Haverkamp, Wolf-Hagen Schunck, Maik Gollasch, Alexander Wutzler

Erschienen in: Cardiovascular Toxicology | Ausgabe 4/2019

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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.
Literatur
1.
Pagidipati, N. J., & Gaziano, T. A. (2013). Estimating deaths from cardiovascular disease: a review of global methodologies of mortality measurement. Circulation, 127, 749–756.CrossRefPubMedPubMedCentral
2.
Mozaffarian, D., Benjamin, E. J., Go, A. S., Arnett, D. K., Blaha, M. J., Cushman, M., … Turner, M. B. (2015). Heart disease and stroke statistics–2015 update: a report from the American Heart Association. Circulation, 131, e29–e322.PubMed
3.
Cleland, J. G., Torabi, A., & Khan, N. K. (2005). Epidemiology and management of heart failure and left ventricular systolic dysfunction in the aftermath of a myocardial infarction. Heart, 91(Suppl 2), ii7–ii13; discussion ii31, ii43-18.PubMedPubMedCentral
4.
Frangogiannis, N. G., Smith, C. W., & Entman, M. L. (2002). The inflammatory response in myocardial infarction. Cardiovascular Research, 53, 31–47.CrossRefPubMed
5.
Eliasz, A. W., Chapman, D., & Ewing, D. F. (1976). Phospholipid phase transitions. Effects of n-alcohols, n-monocarboxylic acids, phenylalkyl alcohols and quaternary ammonium compounds. Biochimica et Biophysica Acta, 448, 220–230.CrossRefPubMed
6.
Schuchardt, J. P., Schmidt, S., Kressel, G., Dong, H., Willenberg, I., Hammock, B. D., Hahn, A., & Schebb, N. H. (2013). Comparison of free serum oxylipin concentrations in hyper- vs. normolipidemic men. Prostaglandins Leukotrienes and Essential Fatty Acids, 89, 19–29.CrossRef
7.
Konkel, A., & Schunck, W. H. (2011). Role of cytochrome P450 enzymes in the bioactivation of polyunsaturated fatty acids. Biochimica et Biophysica Acta, 1814, 210–222.CrossRefPubMed
8.
9.
Imig, J. D., & Hammock, B. D. (2009). Soluble epoxide hydrolase as a therapeutic target for cardiovascular diseases. Nat Rev Drug Discov, 8, 794–805.CrossRefPubMedPubMedCentral
10.
Ozawa, T., Hayakawa, M., Takamura, T., Sugiyama, S., Suzuki, K., Iwata, M., Taki, F., & Tomita, T. (1986). Biosynthesis of leukotoxin, 9,10-epoxy-12 octadecenoate, by leukocytes in lung lavages of rat after exposure to hyperoxia. Biochemical and Biophysical Research Communications, 134, 1071–1078.CrossRefPubMed
11.
Ishizaki, T., Shigemori, K., Nakai, T., Miyabo, S., Ozawa, T., Chang, S. W., & Voelkel, N. F. (1995). Leukotoxin, 9,10-Epoxy-12-Octadecenoate Causes Edematous Lung Injury Via Activation of Vascular Nitric-Oxide Synthase. American Journal of Physiology-Lung Cellular and Molecular Physiology, 269, L65–L70.CrossRef
12.
Sigfried, M. R. A., N.; Lefer, A. M.; Elisseou, E. M.; Zipkin, R.E (1990). Direct cardiovascular actions of two metabolites of linoleic acid. Life Sciences, 46, 427–433.CrossRef
13.
Sugiyama, S., Hayakawa, M., Nagai, S., Ajioka, M., & Ozawa, T. (1987). Leukotoxin, 9, 10-epoxy-12-octadecenoate, causes cardiac failure in dogs. Life Sciences, 40, 225–231.CrossRefPubMed
14.
Li, N., Liu, J. Y., Timofeyev, V., Qiu, H., Hwang, S. H., Tuteja, D., … Chiamvimonvat, N. (2009). Beneficial effects of soluble epoxide hydrolase inhibitors in myocardial infarction model: Insight gained using metabolomic approaches. Journal of Molecular and Cellular Cardiology, 47, 835–845.CrossRefPubMedPubMedCentral
15.
Seubert, J. M., Sinal, C. J., Graves, J., DeGraff, L. M., Bradbury, J. A., Lee, C. R., … Zeldin, D. C. (2006). Role of soluble epoxide hydrolase in postischemic recovery of heart contractile function. Circulation Research, 99, 442–450.CrossRefPubMedPubMedCentral
16.
Hayakawa, M., Kosaka, K., Sugiyama, S., Yokoo, K., Aoyama, H., Izawa, Y., & Ozawa, T. (1990). Proposal of leukotoxin, 9,10-epoxy-12-octadecenoate, as a burn toxin. Biochemistry International, 21, 573–579.PubMed
17.
Kosaka, K., Suzuki, K., Hayakawa, M., Sugiyama, S., & Ozawa, T. (1994). Leukotoxin, a linoleate epoxide: its implication in the late death of patients with extensive burns. Molecular and Cellular Biochemistry, 139, 141–148.CrossRefPubMed
18.
Edin, M. L., Wang, Z., Bradbury, J. A., Graves, J. P., Lih, F. B., DeGraff, L. M., Foley, J. F., Torphy, R., Ronnekleiv, O. K., Tomer, K. B., Lee, C. R., & Zeldin, D. C. (2011). Endothelial expression of human cytochrome P450 epoxygenase CYP2C8 increases susceptibility to ischemia-reperfusion injury in isolated mouse heart. The FASEB Journal, 25, 3436–3447.CrossRefPubMedPubMedCentral
19.
Greene, J. F., Williamson, K. C., Newman, J. W., Morisseau, C., & Hammock, B. D. (2000). Metabolism of monoepoxides of methyl linoleate: bioactivation and detoxification. Archives of Biochemistry and Biophysics, 376, 420–432.CrossRefPubMed
20.
Sakai, T., Ishizaki, T., Ohnishi, T., Sasaki, F., Ameshima, S., Nakai, T., Miyabo, S., Matsukawa, S., Hayakawa, M., & Ozawa, T. (1995). Leukotoxin, 9,10-epoxy-12-octadecenoate inhibits mitochondrial respiration of isolated perfused rat lung. American Journal of Physiology, 269, L326–L331.PubMed
21.
22.
Dudda, A., Spiteller, G., & Kobelt, F. (1996). Lipid oxidation products in ischemic porcine heart tissue. Chemistry and Physics of Lipids, 82, 39–51.CrossRefPubMed
23.
Stimers, J. R., Dobretsov, M., Hastings, S. L., Jude, A. R., & Grant, D. F. (1999). Effects of linoleic acid metabolites on electrical activity in adult rat ventricular myocytes. Biochimica et Biophysica Acta, 1438, 359–368.CrossRefPubMed
24.
Harrell, M. D., & Stimers, J. R. (2002). Differential effects of linoleic Acid metabolites on cardiac sodium current. Journal of Pharmacology and Experimental Therapeutics, 303, 347–355.CrossRefPubMed
25.
Ha, J., Dobretsov, M., Kurten, R. C., Grant, D. F., & Stimers, J. R. (2002). Effect of linoleic acid metabolites on Na(+)/K(+) pump current in N20.1 oligodendrocytes: role of membrane fluidity. Toxicology and Applied Pharmacology, 182, 76–83.CrossRefPubMed
26.
Sisemore, M. F., Zheng, J., Yang, J. C., Thompson, D. A., Plopper, C. G., Cortopassi, G. A., & Hammock, B. D. (2001). Cellular characterization of leukotoxin diol-induced mitochondrial dysfunction. Archives of Biochemistry and Biophysics, 392, 32–37.CrossRefPubMed
27.
Moghaddam, M. F., Grant, D. F., Cheek, J. M., Greene, J. F., Williamson, K. C., & Hammock, B. D. (1997). Bioactivation of leukotoxins to their toxic diols by epoxide hydrolase. Nature Medicine, 3, 562–566.CrossRefPubMed
28.
Lee, J. P., Yang, S. H., Lee, H. Y., Kim, B., Cho, J. Y., Paik, J. H., Oh, Y. J., Kim, D. K., Lim, C. S., & Kim, Y. S. (2012). Soluble epoxide hydrolase activity determines the severity of ischemia-reperfusion injury in kidney. PLoS ONE, 7, e37075.CrossRefPubMedPubMedCentral
29.
Chaudhary, K. R., Zordoky, B. N., Edin, M. L., Alsaleh, N., El-Kadi, A. O., Zeldin, D. C., & Seubert, J. M. (2013). Differential effects of soluble epoxide hydrolase inhibition and CYP2J2 overexpression on postischemic cardiac function in aged mice. Prostaglandins Other Lipid Mediat, 104–105, 8–17.CrossRefPubMed
30.
Mitchell, L. A., Moran, J. H., & Grant, D. F. (2002). Linoleic acid, cis-epoxyoctadecenoic acids, and dihydroxyoctadecadienoic acids are toxic to Sf-21 cells in the absence of albumin. Toxicology Letters, 126, 187–196.CrossRefPubMed
31.
Moran, J. H., Nowak, G., & Grant, D. F. (2001). Analysis of the toxic effects of linoleic acid, 12,13-cis-epoxyoctadecenoic acid, and 12,13-dihydroxyoctadecenoic acid in rabbit renal cortical mitochondria. Toxicology and Applied Pharmacology, 172, 150–161.CrossRefPubMed
32.
Motoki, A., Merkel, M. J., Packwood, W. H., Cao, Z., Liu, L., Iliff, J., Alkayed, N. J., & Van Winkle, D. M. (2008). Soluble epoxide hydrolase inhibition and gene deletion are protective against myocardial ischemia-reperfusion injury in vivo. American Journal of Physiology Heart and Circulatory Physiology, 295, H2128–H2134.CrossRefPubMedPubMedCentral
33.
Viswanathan, S., Hammock, B. D., Newman, J. W., Meerarani, P., Toborek, M., & Hennig, B. (2003). Involvement of CYP 2C9 in mediating the proinflammatory effects of linoleic acid in vascular endothelial cells. Journal of the American College of Nutrition, 22, 502–510.CrossRefPubMed
34.
Di Lisa, F., Canton, M., Menabo, R., Kaludercic, N., & Bernardi, P. (2007). Mitochondria and cardioprotection. Heart Failure Reviews, 12, 249–260.CrossRefPubMed
35.
Spector, A. A., Fang, X., Snyder, G. D., & Weintraub, N. L. (2004). Epoxyeicosatrienoic acids (EETs): metabolism and biochemical function. Progress in Lipid Research, 43, 55–90.CrossRefPubMed
36.
Spector, A. A., & Kim, H. Y. (2015). Cytochrome P450 epoxygenase pathway of polyunsaturated fatty acid metabolism. Biochimica et Biophysica Acta, 1851, 356–365.CrossRefPubMed
37.
Lu, T., VanRollins, M., & Lee, H. C. (2002). Stereospecific activation of cardiac ATP-sensitive K(+) channels by epoxyeicosatrienoic acids: a structural determinant study. Molecular Pharmacology, 62, 1076–1083.CrossRefPubMed
38.
Cabral, M., Martin-Venegas, R., & Moreno, J. J. (2014). Differential cell growth/apoptosis behavior of 13-hydroxyoctadecadienoic acid enantiomers in a colorectal cancer cell line. American Journal of Physiology. Gastrointestinal and Liver Physiology, 307, G664–G671.CrossRefPubMed
Metadaten
Titel
Linoleic Acid Metabolite DiHOME Decreases Post-ischemic Cardiac Recovery in Murine Hearts
verfasst von
Marwin Bannehr
Lena Löhr
Julia Gelep
Wilhelm Haverkamp
Wolf-Hagen Schunck
Maik Gollasch
Alexander Wutzler
Publikationsdatum
06.02.2019
Verlag
Springer US
Erschienen in
Cardiovascular Toxicology / Ausgabe 4/2019
Print ISSN: 1530-7905
Elektronische ISSN: 1559-0259
DOI
https://doi.org/10.1007/s12012-019-09508-x

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