Inhibitors of the 5-Lipoxygenase Pathway in Atherosclerosis

被引：45

作者：

Back, Magnus ^{[1
,2
]}

机构：

[1] Karolinska Univ Hosp, Dept Cardiol, S-17176 Stockholm, Sweden

[2] Karolinska Univ Hosp, Ctr Mol Med, S-17176 Stockholm, Sweden

来源：

CURRENT PHARMACEUTICAL DESIGN | 2009年 / 15卷 / 27期

关键词：

LEUKOTRIENE C-4 SYNTHASE; B-4 RECEPTOR ANTAGONIST; MEMBRANE-ASSOCIATED PROTEINS; COLONY-STIMULATING FACTOR; SMOOTH-MUSCLE-CELLS; GUINEA-PIG LUNG; NF-KAPPA-B; ACTIVATING PROTEIN; CYSTEINYL-LEUKOTRIENES; MYOCARDIAL-INFARCTION;

D O I：

10.2174/138161209789058020

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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 LTC4 synthase, as well as the receptors for leukotriene B-4 (BLT1 and BLT2) 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.

引用

页码：3116 / 3132

页数：17

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