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Review
. 2013 Dec:107:56-63.
doi: 10.1016/j.prostaglandins.2013.02.003. Epub 2013 Mar 6.

Roles of the epoxygenase CYP2J2 in the endothelium

Ara Askari  1 , Scott J Thomson, Matthew L Edin, Darryl C Zeldin, David Bishop-Bailey
Affiliations
Review

Roles of the epoxygenase CYP2J2 in the endothelium

Ara Askari et al. Prostaglandins Other Lipid Mediat. 2013 Dec.

Abstract

Cytochrome p450 (CYP)2J2 is an epoxygenase enzyme that metabolises arachidonic acid to epoxyeicosatrienoic acids (EETs). EETs are inactivated by soluble epoxide hydrolase (sEH), which converts them in to their corresponding dihydroxyeicosatrienoic acids (DHETs). CYP2J2 is highly expressed in cardiovascular tissue including the heart and vascular endothelial cells. CYP2J2 and the EETs it produces have been shown to have a diverse range of effects on the vasculature, including the regulation of inflammation, vascular tone, cellular proliferation, angiogenesis, and metabolism. This review will examine these established and emerging roles of CYP2J2 in the biology of vascular endothelial cells.

Keywords: Angiogenesis; Dilation; Endothelial; Epoxygenase; Inflammation; Metabolism.

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Figures

Figure 1
Figure 1. Actions of CYP2J2 in endothelial cells
CYP2J2 produces mediators that can vasodilate via ATP-sensitive K+ channels leading to hyperpolarisation of underlying smooth muscle cells and up-regulate endothelial nitric oxide synthase (eNOS; NOS-3) protein and activity. CYP2J products may also vasoconstrict different vascular beds by activating the thromboxane A2 (TXA2) receptor or via transient receptor potential (TRP) channels. In addition, CYP2J and its products have anti-platelet/anti-coagulant properties via upregulation of tissue plasminogen activator (tPA), NOS, and through a reduction in TXA2 synthesis, a decrease in p-selectin expression, a decrease in intracellular Ca2+ and via platelet hyperpolarisation. CY2J enzymes can metabolise a variety of xenobiotics and drugs to inactivate them, and is anti-inflammatory decreasing NF-κB activation and its target genes including VCAM-1, e-selectin, monocytes chemoattractant protein (MCP)-1 (CCL2), IL-1β and IL-6. CYP2J and its products are angiogenic by increasing VEGF, FGF2, EGF, eNOS, sphingosine kinase (SK-1), and STAT-3 in part via activation of Akt, Forkhead box (FOX)O, and SRC tyrosine kinase, and is cytoprotective being associated with a reduction in intracellular superoxide generation and oxidant stress.
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