| Reno-protective mechanisms of epoxyeicosatrienoic acids in cardiovascular disease. | |
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MedLine Citation:
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PMID: 22116511 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cardiovascular disease (CVD) is the leading cause of mortality worldwide, and it is well known that end-stage renal disease (ESRD) is a profound consequence of the progression of CVD. Present treatments only slow CVD progression to ESRD, and it is imperative that new therapeutic strategies are developed to prevent the incidence of ESRD. Because epoxyeicosatrienoic acids (EETs) have been shown to elicit reno-protective effects in hypertensive animal models, the current review will focus on addressing the reno-protective mechanisms of EETs in CVD. The cytochrome P-450 epoxygenase catalyzes the oxidation of arachidonic acid to EETs. EETs have been identified as endothelium-derived hyperpolarizing factors (EDHFs) with vasodilatory, anti-inflammatory, antihypertensive, and antiplatelet aggregation properties. EETs also have profound effects on vascular migration and proliferation and promote angiogenesis. The progression of CVD has been linked to decreased EETs levels, leading to the concept that EETs should be therapeutically targeted to prevent end-organ damage associated with CVD. However, EETs are quickly degraded by the enzyme soluble epoxide hydrolase (sEH) to their less active diols, dihydroxyeicosatrienoic acids (DHETs). As such, one way to increase EETs level is to inhibit their degradation to DHETs by using sEH inhibitors. Inhibition of sEH has been shown to effectively reduce blood pressure and organ damage in experimental models of CVD. Another approach to target EETs is to develop EET analogs with improved solubility and resistance to auto-oxidation and metabolism by sEH. For example, stable ether EET analogs dilate afferent arterioles and lower blood pressure in hypertensive rodent animal models. EET agonists also improve insulin signaling and vascular function in animal models of metabolic syndrome. |
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Authors:
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Ahmed A Elmarakby |
Publication Detail:
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Type: Historical Article; Journal Article; Research Support, Non-U.S. Gov't; Review Date: 2011-11-23 |
Journal Detail:
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Title: American journal of physiology. Regulatory, integrative and comparative physiology Volume: 302 ISSN: 1522-1490 ISO Abbreviation: Am. J. Physiol. Regul. Integr. Comp. Physiol. Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-02-13 Completed Date: 2012-04-19 Revised Date: 2012-05-23 |
Medline Journal Info:
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Nlm Unique ID: 100901230 Medline TA: Am J Physiol Regul Integr Comp Physiol Country: United States |
Other Details:
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Languages: eng Pagination: R321-30 Citation Subset: IM |
Affiliation:
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Department of Oral Biology, Division of Pharmacology, Georgia Health Sciences University, Augusta, USA. aelmarakby@georgiahealth.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arachidonic Acids / metabolism Awards and Prizes* Cardiovascular Diseases / metabolism* Disease Models, Animal Eicosanoids / agonists, metabolism* Epoxide Hydrolases / antagonists & inhibitors, metabolism Epoxy Compounds History, 21st Century Humans Kidney Failure, Chronic / metabolism, prevention & control* Physiology / history* United States |
| Chemical | |
Reg. No./Substance:
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0/Arachidonic Acids; 0/Eicosanoids; 0/Epoxy Compounds; EC 3.3.2.-/Epoxide Hydrolases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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