| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2564287 | Pharmacology & Therapeutics | 2006 | 12 Pages |
Abstract
The activation of CYP epoxygenases in endothelial cells is an important step in the nitric oxide and prostacyclin (PGI2)-independent vasodilatation of several vascular beds and EETs have been identified as endothelium-derived hyperpolarizing factors (EDHFs). However, in addition to regulating vascular tone, EETs modulate several signaling cascades and affect cell proliferation, cell migration, and angiogenesis. Signaling molecules modulated by EETs include tyrosine kinases and phosphatases, mitogen-activated protein kinases, protein kinase A (PKA), cyclooxygenase (COX)-2, and several transcription factors. This review summarizes the role of CYP-derived EETs in cell signaling and focuses particularly on their role as intracellular amplifiers of endothelial cell hyperpolarization as well as in cell proliferation and angiogenesis. The angiogenic properties of CYP epoxygenases and CYP-derived EETs implicate that these enzymes may well be accessible targets for anti-angiogenic as well as angiogenic therapies.
Keywords
hyperpolarizationPI 3-KCa2+-dependent K+ channelsPGI2EDHFVCAM-1PLA2ERK 1/2HB-EGFPDGFPKCpKaPPARαICAM-1bFGFCyPTrpNF-κBCOXMMPEGFJnk3′,5′-cyclic adenosine monophosphatecyclic AMPc-Jun N-terminal kinaseDHETsEHcyclooxygenasephospholipase A2Angiogenesisepoxyeicosatrienoic aciddihydroxyeicosatrienoic acidhydroxyeicosatetraenoic acidEndotheliumeicosanoidsEETCytochrome P450epidermal growth factorVascular Endothelial Growth Factor (VEGF)platelet-derived growth factorVascular endothelial cell growth factorbasic fibroblast growth factorHeparin-binding EGF-like growth factornuclear factor κBEndothelium-derived hyperpolarizing factorPhosphatidylinositol 3-kinaseMatrix metalloproteasesintercellular adhesion molecule-1vascular cell adhesion molecule-1Signal transductionHETESoluble epoxide hydrolaseMembrane potentialtransient receptor potentialprotein kinase AProtein kinase CprostacyclinBKCa channelsPeroxisome proliferator activated receptor α
Related Topics
Health Sciences
Pharmacology, Toxicology and Pharmaceutical Science
Pharmacology
Authors
U. Ruth Michaelis, Ingrid Fleming,