Article ; Online: Role of cytochrome P450-epoxygenase and soluble epoxide hydrolase in the regulation of vascular response.
Advances in pharmacology (San Diego, Calif.)
2023 Volume 97, Page(s) 37–131
Abstract: The role of cytochrome P450-epoxygenase has been seen in cardiovascular physiology and pathophysiology. The aberration in CYP450-epoxygenase genes occur due to genetic polymorphisms, aging, or environmental factors, that increase susceptibility to ... ...
Abstract | The role of cytochrome P450-epoxygenase has been seen in cardiovascular physiology and pathophysiology. The aberration in CYP450-epoxygenase genes occur due to genetic polymorphisms, aging, or environmental factors, that increase susceptibility to cardiovascular diseases (CVDs). The actual role played by the CYP450-epoxygenases is the metabolism of arachidonic acid (AA) and linoleic acid (LA) into epoxyeicosatrienoic acids (EETs) and epoxyoctadecaenoic acid (EpOMEs) metabolites (oxylipins) and others, which is involved in vasodilation and myocardial-protection. But the genetic polymorphisms in CYP450-epoxygenases lose their beneficial cardiovascular effects of oxylipins, and the soluble epoxide hydrolase (sEH) antagonizes beneficial oxylipins into diols. Like sEH converts EETs into dihydroxyeicosatrienoic acid (DHETs), EpOMEs into dihydroxyoctadecaenoic acid (DiHOMEs), and reverses its beneficial effects, and the sEH gene (Ephx2) polymorphisms cause the enzyme to become overactive and convert epoxy-fatty acids into diols, making them vulnerable to CVDs, including hypertension. Other, enzymes like ω-hydroxylases (CYP450-4A11 & CYP450-4F2)-derived oxylipins from AA, ω-terminal-hydroxyeicosatetraenoic acids (19-, 20-HETE), lipoxygenase-derived oxylipins, mid-chain hydroxyeicosatetraenoic acids (5-, 11-, 12-, 15-HETEs), and the cyclooxygenase-derived prostanoids (prostaglandins: PGD |
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MeSH term(s) | Humans ; Animals ; Mice ; Cytochrome P-450 CYP2J2 ; Epoxide Hydrolases/genetics ; Epoxide Hydrolases/metabolism ; Oxylipins/metabolism ; Cytochrome P-450 Enzyme System/genetics ; Cytochrome P-450 Enzyme System/metabolism ; Cardiovascular Diseases/genetics ; Hydroxyeicosatetraenoic Acids ; Hypertension |
Chemical Substances | Cytochrome P-450 CYP2J2 (EC 1.14.14.1) ; Epoxide Hydrolases (EC 3.3.2.-) ; Oxylipins ; Cytochrome P-450 Enzyme System (9035-51-2) ; Hydroxyeicosatetraenoic Acids |
Language | English |
Publishing date | 2023-01-02 |
Publishing country | United States |
Document type | Journal Article ; Research Support, N.I.H., Extramural |
ISSN | 1557-8925 |
ISSN (online) | 1557-8925 |
DOI | 10.1016/bs.apha.2022.12.003 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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