Abstract
The inflammatory environment within the atherosclerotic lesion stimulates the 5-lipoxygenase pathway of arachidonic acid metabolism, leading to the biosynthesis of the potent lipid inflammatory mediators leukotrienes. The present review summarizes the components of this pathway; the enzymes 5-lipoxygenase (5-LO, ALOX5) with its activating protein, FLAP (ALOX5AP), LTA(4) hydrolase and LTC(4) synthase, as well as the receptors for leukotriene B(4) (BLT(1) and BLT(2)) and cysteinyl-leukotrienes (CysLT(1) and CysLT(2)), respectively. Genetic variations within the genes encoding these proteins have been associated with cardiovascular risk. Inhibiting the 5-lipoxygenase pathway through either leukotriene synthesis inhibitors or leukotriene receptor antagonists in experimental models of atherosclerosis has however generated contradictory results. Several inhibitors of the 5-lipoxygenase pathway are now evaluated in clinical trials of patients with cardiovascular disease.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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5-Lipoxygenase-Activating Proteins
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Animals
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Anti-Inflammatory Agents / pharmacology
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Anti-Inflammatory Agents / therapeutic use*
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Arachidonate 5-Lipoxygenase / genetics
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Arachidonate 5-Lipoxygenase / metabolism
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Atherosclerosis / drug therapy*
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Atherosclerosis / enzymology
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Atherosclerosis / genetics
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Carrier Proteins / antagonists & inhibitors
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Carrier Proteins / metabolism
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Drug Design
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Epoxide Hydrolases / antagonists & inhibitors
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Epoxide Hydrolases / metabolism
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Glutathione Transferase / antagonists & inhibitors
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Glutathione Transferase / metabolism
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Humans
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Hypolipidemic Agents / pharmacology
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Hypolipidemic Agents / therapeutic use*
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Inflammation / drug therapy*
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Inflammation / enzymology
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Inflammation / genetics
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Leukotriene Antagonists / therapeutic use
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Lipoxygenase Inhibitors* / pharmacology
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Lipoxygenase Inhibitors* / therapeutic use*
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Membrane Proteins / antagonists & inhibitors
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Membrane Proteins / metabolism
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Receptors, Leukotriene / drug effects
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Receptors, Leukotriene / metabolism
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Receptors, Leukotriene B4 / antagonists & inhibitors
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Receptors, Leukotriene B4 / metabolism
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Signal Transduction / drug effects*
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Signal Transduction / genetics
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Treatment Outcome
Substances
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5-Lipoxygenase-Activating Proteins
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ALOX5AP protein, human
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Anti-Inflammatory Agents
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Carrier Proteins
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Hypolipidemic Agents
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Leukotriene Antagonists
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Lipoxygenase Inhibitors
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Membrane Proteins
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Receptors, Leukotriene
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Receptors, Leukotriene B4
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cysteinyl leukotriene receptor 2
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Arachidonate 5-Lipoxygenase
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Glutathione Transferase
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Epoxide Hydrolases
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leukotriene-C4 synthase
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leukotriene D4 receptor
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leukotriene A4 hydrolase