The role of 14,15-dihydroxyeicosatrienoic acid levels in inflammation and its relationship to lipoproteins
- PMID: 24148690
- PMCID: PMC3874761
- DOI: 10.1186/1476-511X-12-151
The role of 14,15-dihydroxyeicosatrienoic acid levels in inflammation and its relationship to lipoproteins
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
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- Michaelis UR, Fisslthaler B. et al. Cytochrome P450 2C9-derived epoxyeicosatrienoic acids induce angiogenesis via cross-talk with the epidermal growth factor receptor (EGFR) FASEB J. 2003;17(6):770–772. - PubMed
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- Fitzpatrick FA, Ennis MD. et al. Inhibition of cyclooxygenase activity and platelet aggregation by epoxyeicosatrienoic acids. Influence of stereochemistry. J Biol Chem. 1986;261:15334–15338. - PubMed
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