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Cytochrome P450-derived fatty acid epoxides and diols in angiogenesis and stem cell biology.
Frömel, Timo; Naeem, Zumer; Pirzeh, Lale; Fleming, Ingrid.
  • Frömel T; Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Frankfurt am Main, Germany.
  • Naeem Z; Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Frankfurt am Main, Germany.
  • Pirzeh L; Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Frankfurt am Main, Germany.
  • Fleming I; Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Frankfurt am Main, Germany; German Centre for Cardiovascular Research (DZHK) Partner Site Rhein-Main, Frankfurt am Main, Germany; The Cardio-Pulmonary Institute, Frankfurt am Main, Germany. Electronic address: flemi
Pharmacol Ther ; 234: 108049, 2022 06.
Article in English | MEDLINE | ID: covidwho-1536989
ABSTRACT
Cytochrome P450 (CYP) enzymes are frequently referred to as the third pathway for the metabolism of arachidonic acid. While it is true that these enzymes generate arachidonic acid epoxides i.e. the epoxyeicosatrienoic acids (EETs), they are able to accept a wealth of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) to generate a large range of regio- and stereo-isomers with distinct biochemical properties and physiological actions. Probably the best studied are the EETs which have well documented effects on vascular reactivity and angiogenesis. CYP enzymes can also participate in crosstalk with other PUFA pathways and metabolize prostaglandin G2 and H2, which are the precursors of effector prostaglandins, to affect macrophage function and lymphangiogenesis. The activity of the PUFA epoxides is thought to be kept in check by the activity of epoxide hydrolases. However, rather than being inactive, the diols generated have been shown to regulate neutrophil activation, stem and progenitor cell proliferation and Notch signaling in addition to acting as exercise-induced lipokines. Excessive production of PUFA diols has also been implicated in pathologies such as severe respiratory distress syndromes, including COVID-19, and diabetic retinopathy. This review highlights some of the recent findings related to this pathway that affect angiogenesis and stem cell biology.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Epoxy Compounds / COVID-19 Limits: Humans Language: English Journal: Pharmacol Ther Year: 2022 Document Type: Article Affiliation country: J.pharmthera.2021.108049

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Epoxy Compounds / COVID-19 Limits: Humans Language: English Journal: Pharmacol Ther Year: 2022 Document Type: Article Affiliation country: J.pharmthera.2021.108049