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

Lipids Health Dis. 2013 Oct 23;12:151. doi: 10.1186/1476-511X-12-151.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8,11,14-Eicosatrienoic Acid / analogs & derivatives*
  • 8,11,14-Eicosatrienoic Acid / blood
  • Aged
  • C-Reactive Protein / metabolism*
  • Case-Control Studies
  • Cholesterol, HDL / blood*
  • Cholesterol, LDL / blood*
  • Coronary Disease / blood*
  • Coronary Disease / pathology
  • Cytochrome P-450 CYP2J2
  • Cytochrome P-450 Enzyme System / blood
  • Female
  • Humans
  • Inflammation / blood
  • Inflammation / pathology
  • Male
  • Middle Aged
  • Statistics, Nonparametric
  • Triglycerides / blood

Substances

  • 14,15-dihydroxyeicosatrienoic acid
  • CYP2J2 protein, human
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Triglycerides
  • 14,15-epoxy-5,8,11-eicosatrienoic acid
  • C-Reactive Protein
  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 CYP2J2
  • 8,11,14-Eicosatrienoic Acid