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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Inhibitors of the 5-Lipoxygenase Pathway in Atherosclerosis

Author(s): Magnus Back

Volume 15 , Issue 27 , 2009

Page: [3116 - 3132] Pages: 17

DOI: 10.2174/138161209789058020

Price: $65

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), LTA4 hydrolase and LTC4 synthase, as well as the receptors for leukotriene B4 (BLT1 and BLT2) and cysteinyl-leukotrienes (CysLT1 and CysLT2), 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.


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