The Role of 14,15-dihydroxyeicosatrienoic Acid Levels in Inflammation and Its Relationship to Lipoproteins

Overview

Journal Lipids Health Dis

Publisher Biomed Central

Specialties Biochemistry
Endocrinology

Date 2013 Oct 24

PMID 24148690

Citations 28

Authors

Tian Yang

Ran Peng

Yuan Guo

Li Shen

Shuiping Zhao

Danyan Xu

Affiliations

Soon will be listed here.

Abstract

Background: 14,15-Epoxyeicosatrienoic acids (14,15-EETs) generated from arachidonic acid by cytochrome P450 epoxygenases have beneficial effects in certain cardiovascular diseases, and increased 14,15-EET levels protect the cardiovascular system. 14,15-EETs are rapidly hydrolyzed by soluble epoxide hydrolase (sEH) to the corresponding 14,15-dihydroxyeicosatrienoic acids (14,15-DHETs), which are generally less biologically active but more stable metabolite. A functionally relevant polymorphism of the CYP2J2 gene is independently associated with an increased risk of coronary heart disease (CHD), and the major CYP2J2 product is 14,15-EETs. 14,15-DHETs can be considered a relevant marker of CYP2J2 activity. Therefore, the aim of the present study was to evaluate the plasma 14,15-DHET levels to reflect the 14,15-EET levels in an indirectly way in patients with CHD, and to highlight the growing body of evidence that 14,15-EETs also play a role in anti-inflammatory and lipid-regulating effects in patients with CHD. This was achieved by investigating the relationship between 14,15-DHETs and high-sensitivity C-reactive protein (hs-CRP) and blood lipoproteins.

Methods: Samples of peripheral venous blood were drawn from 60 patients with CHD and 60 healthy controls. A 14,15-DHET enzyme-linked immunosorbent assay kit (14,15-DHET ELISA kit) was used to measure the plasma 14,15-DHET levels. Hs-CRP, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein-cholesterol levels were measured.

Results: 14,15-DHET levels (2.53 ± 1.60 ng/mL) were significantly higher in patients with CHD as compared with those of the healthy controls (1.65 ± 1.54 ng/mL, P < 0.05). There was a significant positive correlation between 14,15-DHETs and hs-CRP levels (R = 0.286, P = 0.027). However, there was no significant correlation between 14,15-DHETs and blood lipoproteins (all, P > 0.05).

Conclusions: Increased plasma 14,15-DHET levels reflect the decreased of 14,15-EET levels in an indirectly way. Indicated that decreased plasma 14,15-EET levels might be involved in the inflammatory reaction process in atherosclerosis.

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References

Pritchard Jr K, Wong P, Stemerman M . Atherogenic concentrations of low-density lipoprotein enhance endothelial cell generation of epoxyeicosatrienoic acid products. Am J Pathol. 1990; 136(6):1383-91. PMC: 1877592. View

Fang X, Moore S, Stoll L, Rich G, Kaduce T, Weintraub N . 14,15-Epoxyeicosatrienoic acid inhibits prostaglandin E2 production in vascular smooth muscle cells. Am J Physiol. 1998; 275(6):H2113-21. DOI: 10.1152/ajpheart.1998.275.6.H2113. View

McQueen M, Hawken S, Wang X, Ounpuu S, Sniderman A, Probstfield J . Lipids, lipoproteins, and apolipoproteins as risk markers of myocardial infarction in 52 countries (the INTERHEART study): a case-control study. Lancet. 2008; 372(9634):224-33. DOI: 10.1016/S0140-6736(08)61076-4. View

Schnell-Inderst P, Schwarzer R, Gohler A, Grandi N, Grabein K, Stollenwerk B . Prognostic value, clinical effectiveness, and cost-effectiveness of high-sensitivity C-reactive protein as a marker for major cardiac events in asymptomatic individuals: a health technology assessment report. Int J Technol Assess Health Care. 2010; 26(1):30-9. DOI: 10.1017/S0266462309990870. View

Gordon T, CASTELLI W, Hjortland M, Kannel W, DAWBER T . High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med. 1977; 62(5):707-14. DOI: 10.1016/0002-9343(77)90874-9. View

Schlager O, Exner M, Mlekusch W, Sabeti S, Amighi J, Dick P . C-reactive protein predicts future cardiovascular events in patients with carotid stenosis. Stroke. 2007; 38(4):1263-8. DOI: 10.1161/01.STR.0000259890.18354.d2. View

Hokanson J, Austin M . Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk. 1996; 3(2):213-9. View

Poss J, Custodis F, Werner C, Weingartner O, Bohm M, Laufs U . Cardiovascular disease and dyslipidemia: beyond LDL. Curr Pharm Des. 2011; 17(9):861-70. DOI: 10.2174/138161211795428858. View

Nithipatikom K, Moore J, Isbell M, Falck J, Gross G . Epoxyeicosatrienoic acids in cardioprotection: ischemic versus reperfusion injury. Am J Physiol Heart Circ Physiol. 2006; 291(2):H537-42. DOI: 10.1152/ajpheart.00071.2006. View

10.

Xu D, Davis B, Wang Z, Zhao S, Wasti B, Liu Z . A potent soluble epoxide hydrolase inhibitor, t-AUCB, acts through PPARγ to modulate the function of endothelial progenitor cells from patients with acute myocardial infarction. Int J Cardiol. 2012; 167(4):1298-304. PMC: 3821736. DOI: 10.1016/j.ijcard.2012.03.167. View

11.

Schuck R, Theken K, Edin M, Caughey M, Bass A, Ellis K . Cytochrome P450-derived eicosanoids and vascular dysfunction in coronary artery disease patients. Atherosclerosis. 2013; 227(2):442-8. PMC: 3638946. DOI: 10.1016/j.atherosclerosis.2013.01.034. View

12.

Spector A, Fang X, Snyder G, Weintraub N . Epoxyeicosatrienoic acids (EETs): metabolism and biochemical function. Prog Lipid Res. 2003; 43(1):55-90. DOI: 10.1016/s0163-7827(03)00049-3. View

13.

Biasucci L, Santamaria M, Liuzzo G . [Inflammation, atherosclerosis and acute coronary syndromes]. Minerva Cardioangiol. 2002; 50(5):475-86. View

14.

Chen J, Wang D, Falck J, Capdevila J, Harris R . Transfection of an active cytochrome P450 arachidonic acid epoxygenase indicates that 14,15-epoxyeicosatrienoic acid functions as an intracellular second messenger in response to epidermal growth factor. J Biol Chem. 1999; 274(8):4764-9. DOI: 10.1074/jbc.274.8.4764. View

15.

Barter P . HDL-C: role as a risk modifier. Atheroscler Suppl. 2011; 12(3):267-70. DOI: 10.1016/S1567-5688(11)70885-6. View

16.

Imig J, Hammock B . Soluble epoxide hydrolase as a therapeutic target for cardiovascular diseases. Nat Rev Drug Discov. 2009; 8(10):794-805. PMC: 3021468. DOI: 10.1038/nrd2875. View

17.

Newman J, Morisseau C, Harris T, Hammock B . The soluble epoxide hydrolase encoded by EPXH2 is a bifunctional enzyme with novel lipid phosphate phosphatase activity. Proc Natl Acad Sci U S A. 2003; 100(4):1558-63. PMC: 149871. DOI: 10.1073/pnas.0437724100. View

18.

Michaelis U, Fisslthaler B, Medhora M, Harder D, Fleming I, Busse R . Cytochrome P450 2C9-derived epoxyeicosatrienoic acids induce angiogenesis via cross-talk with the epidermal growth factor receptor (EGFR). FASEB J. 2003; 17(6):770-2. DOI: 10.1096/fj.02-0640fje. View

19.

Theken K, Schuck R, Edin M, Tran B, Ellis K, Bass A . Evaluation of cytochrome P450-derived eicosanoids in humans with stable atherosclerotic cardiovascular disease. Atherosclerosis. 2012; 222(2):530-6. PMC: 3361525. DOI: 10.1016/j.atherosclerosis.2012.03.022. View

20.

Krotz F, Riexinger T, Buerkle M, Nithipatikom K, Gloe T, Sohn H . Membrane-potential-dependent inhibition of platelet adhesion to endothelial cells by epoxyeicosatrienoic acids. Arterioscler Thromb Vasc Biol. 2004; 24(3):595-600. DOI: 10.1161/01.ATV.0000116219.09040.8c. View