The role of 14,15-dihydroxyeicosatrienoic acid levels in inflammation and its relationship to lipoproteins

Abstract

Background14,15-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.MethodsSamples 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.Results14,15-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).ConclusionsIncreased 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.

Genetic deletion of 12/15 lipoxygenase promotes effective resolution of inflammation following myocardial infarction

“…In arachidonate cascade, the P450 epoxygenase is unique in regio- and stereochemical selectivity to biosynthesize EET mediators. EETs are known to reduce infarct size, preserve LV function and limit cardiac hypertrophy [35, 36]. CYP2J subfamilies of CYP are abundantly expressed in the cardiovascular system and metabolize AA to produce four biologically active EETs: 5,6 (cypoxins; CExn1)-, 8,9 (CExn2)-, 11,12 (CExn3)-, and 14,15 (CExn4)-EETs [37].…”

“…These results the align with the results from Yang et al . [35] where a decrease in EETs generated an inflammatory response in coronary heart disease (CHD) patients. Other clinical studies have also shown obstructive coronary artery disease (CAD) is associated with lower EET metabolite levels [38].…”

Effects of fish oil supplementation on prostaglandins in normal and tumor colon tissue: modulation by the lipogenic phenotype of colon tumors

“…AA oxygenation by cytochrome P450 forms epoxyeicosatrienoic acids, and epoxide hydrolase subsequently results in formation of the more stable 14,15-DHETs (Figure 1). These compounds have been associated with pro-inflammatory processes [36, 37]. Neither 14,15-S and 14,15-R DHET were significantly altered by diet in normal tissues, but both products were reduced in colon tumors of fish oil-fed animals versus that of Western fat-fed animals (Table 1).…”

Downregulated Serum 14, 15-Epoxyeicosatrienoic Acid Is Associated With Abdominal Aortic Calcification in Patients With Primary Aldosteronism

“…An enzyme-linked immunosorbent assay (ELISA) was used to measure the plasma 14, 15-DHET (14, 15-DHET ELISA kit; Detroit R&D Inc., Detroit, MI, USA) according to the manual. 26…”