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Review
, 80 (1), 28-44

The Role of Epoxyeicosatrienoic Acids in the Cardiovascular System

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Review

The Role of Epoxyeicosatrienoic Acids in the Cardiovascular System

L Yang et al. Br J Clin Pharmacol.

Abstract

There is increasing evidence suggesting that epoxyeicosatrienoic acids (EETs) play an important role in cardioprotective mechanisms. These include regulating vascular tone, modulating inflammatory responses, improving cardiomyocyte function and reducing ischaemic damage, resulting in attenuation of animal models of cardiovascular risk factors. This review discusses the current knowledge on the role of EETs in endothelium-dependent control of vascular tone in the healthy and in subjects with cardiovascular risk factors, and considers the pharmacological potential of targeting this pathway.

Keywords: cardiovascular system; epoxyeicosatrienoic acids; soluble epoxide hydrolase inhibitor; vascular tone.

Figures

Figure 1
Figure 1
Mechanisms of endothelial dependent vasodilatation mediated by nitric oxide, prostacyclin and endothelium derived hyperpolarizing factors. Pharmacological agonists can bind to endothelial receptors and stimulate the release of these factors in a calcium dependent manner. The vasodilating factors act on the smooth muscle and mediate vasodilatation by mechanisms shown in Figure 2. R, receptor; M1 and M3, muscarinic receptors; B2, bradykinin receptor; Ca2+, calcium ions; NOS, nitric oxide synthase; NO, nitric oxide; GC, guanylate cyclase; cGMP, cyclic guanosine monophosphate; PGI2, prostacyclin; AC, adenylate cyclase; cAMP, cyclic adenylate monophosphate; EDHF, endothelium derived hyperpolarising factor; EET, epoxyeicosatrienoic acid; H2O2, hydrogen peroxide; K+, potassium ions
Figure 2
Figure 2
The diagram shows that both EDHF and NO mediate smooth muscle relaxation by reducing smooth muscle cell intracellular calcium, whereas PGI2 mediates relaxation via a calcium independent mechanism. EDHF, endothelium derived hyperpolarising factor; K+, potassium; NO, nitric oxide; cGMP, cyclic guanosine monophosphate; PKG, cGMP- dependent protein kinase; PGI2, prostacyclin; cAMP, cyclic adenylate monophospate; PKA, cAMP- dependent protein kinase; Ca2+, calcium; MLCK, myosin light chain kinase; MLC, myosin light chain
Figure 3
Figure 3
Arachidonic acid is liberated from phospholipids by phospholipase A2 enzyme. There are many products of arachidonic acid metabolism and EETs are products of cytochrome P450 enzymes. There are four regio-isomers of EETs. In vivo, the majority of EETs are readily hydrolyzed by soluble epoxide hydrolase enzymes to their corresponding DHETs. HETE, hydroxyyl-eicosatetraenoic acid; EET, epoxyeicosatrienoic acid; sEH, soluble epoxide hydrolase; DHET, dihydroxyepoxyeicosatrienoic acid
Figure 4
Figure 4
This diagram shows the mechanisms by which EETs exert hyperpolarization effects on the endothelial cell and the smooth muscle cell. Agonist binding to a luminal receptor of the endothelial cell activates phospholipase A in a calcium dependent manner, which converts phospholipids to arachidonic acid. EETs are products of CYP450 enzyme metabolism. EETs may activate the IKCa and SKCa channels via TRPV4 channels. EETs may activate BKCa and KATP channels via an EET receptor or via TRPV4 channels. R, receptor; M1 and M3, muscarinic receptors; B2, bradykinin recetor; Ca2+, calcium ions; NOS, nitric oxide synthase; NO, nitric oxide; GC, guanylate cyclase; cGMP, cyclic guanosine monophosphate; PL, phospholipids; PLA2, phospholipase A2; AA, arachidonic acid; CYP, cytochrome P450 enzymes; K+, potassium ions; BK, large conductance calcium-dependent potassium channel; KATP, ATP sensitive potassium channel; TRP, transient receptor potential channels, RGS, G-protein coupled receptor coupled; cAMP, cyclic adenylate monophosphate

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References

    1. World Health Organization. Major causes of death. Available at http://www.who.int/mediacentre/factsheets/fs310/en/index2.html (last accessed 22 March 2014)
    1. British Heart Foundation. Cardiovascular diseases statistics. Available at http://www.bhf.org.uk/heart-health/heart-statistics.aspx (last accessed 22 March 2014)
    1. Ross MH, Pawlina W. Histology: a Text and Atlas. 6th Ed. Baltimore: Wolters Kluwer Lippincott Williams & Wilkins; 2011. pp. 400–30. Chapter 13.
    1. Furchgott RF, Zawadzki JW. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980;288:373–6. - PubMed
    1. Dusting GJ, Moncada S, Vane JR. Prostacyclin (PGX) is the endogenous metabolite responsible for relaxation of coronary arteries induced by arachindonic acid. Prostaglandins. 1977;13:3–15. - PubMed

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