| Cytochrome P450 and arachidonic acid metabolites: role in myocardial ischemia/reperfusion injury revisited. | |
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MedLine Citation:
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PMID: 15993870 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Ischemia-reperfusion of the heart and other organs results in the accumulation of unesterified arachidonic acid (AA) via the action of membrane-bound phospholipases, primarily phospholipase A2. AA can be metabolized by the classical cyclooxygenase (COX) and lipoxygenase (LOX) pathways to well-characterized metabolites and their respective cardioprotective end products such as prostacyclin (PGI2) and 12-hydroxyeicosatetraenoic acid (12-HETE). However, it has only been recently recognized that another less well-characterized pathway of AA metabolism, the cytochrome P450 (CYP) pathway, may have important cardiovascular effects. Several lines of data support the possibility that certain CYP metabolites resulting from the hydroxylation of AA such as 20-hydroxyeicosatetraenoic acid (20-HETE) are potent vasoconstrictors and may produce detrimental effects in the heart during ischemia and pro-inflammatory effects during reperfusion. On the other hand, a group of regioisomers resulting from the epoxidation of AA, including 5,6-, 8,9-, 11,12- and 14,15-epoxyeicosatrienoic acid (EETs), have been shown to reduce ischemic and/or reperfusion injury in the heart and vasculature. This review will discuss the detrimental and beneficial actions, including the potential cellular mechanisms responsible as a result of stimulating or inhibiting the two arms of this novel CYP pathway. The therapeutic potential of increasing EET concentrations and/or reducing 20-HETE concentrations will also be addressed. |
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Authors:
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Garrett J Gross; John R Falck; Eric R Gross; Marilyn Isbell; Jeannine Moore; Kasem Nithipatikom |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Cardiovascular research Volume: 68 ISSN: 0008-6363 ISO Abbreviation: Cardiovasc. Res. Publication Date: 2005 Oct |
Date Detail:
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Created Date: 2005-09-09 Completed Date: 2006-02-09 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 18-25 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. ggross@mcw.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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8,11,14-Eicosatrienoic Acid
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metabolism Adenosine Triphosphate / metabolism Animals Arachidonic Acid / metabolism* Cytochrome P-450 Enzyme System / physiology* Humans Hydroxyeicosatetraenoic Acids / metabolism Myocardial Reperfusion Injury / metabolism* Myocardium / metabolism* Potassium Channels / metabolism Prostaglandins / metabolism Signal Transduction |
| Grant Support | |
ID/Acronym/Agency:
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HL074314-03/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Hydroxyeicosatetraenoic Acids; 0/Potassium Channels; 0/Prostaglandins; 506-32-1/Arachidonic Acid; 56-65-5/Adenosine Triphosphate; 7324-41-6/8,11,14-Eicosatrienoic Acid; 79551-86-3/20-hydroxy-5,8,11,14-eicosatetraenoic acid; 9035-51-2/Cytochrome P-450 Enzyme System |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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