Whatling Carl, McPheat William, Herslöf Margareta
AstraZeneca R&D Mölndal, Bioscience Department, Pepparedsleden 1, 431 83 Mölndal, Sweden.
Expert Opin Investig Drugs. 2007 Dec;16(12):1879-93. doi: 10.1517/13543784.16.12.1879.
The 5-lipoxygenase pathway is responsible for the production of leukotrienes--inflammatory lipid mediators that have a role in innate immunity, but that can also have pathological effects in inflammatory diseases. Recently, a potential link between leukotriene production and atherosclerosis has been proposed. The expression of leukotriene biosynthetic enzymes and leukotriene receptors has been identified in coronary and carotid atherosclerotic plaques, and the levels of biosynthetic enzymes have been correlated with the clinical symptoms of unstable plaques. Genetic variants in 5-lipoxygenase pathway genes have also been associated with a relative risk of developing myocardial infarction and stroke. On the basis of these discoveries, antileukotriene compounds are now being evaluated for the treatment of cardiovascular disease. Several tool compounds have been shown to limit the progression of lesion development in preclinical models of atherosclerosis, and three compounds, including two drugs previously developed for asthma, are undergoing clinical trials in patients with acute coronary syndromes.
5-脂氧合酶途径负责白三烯的生成，白三烯是一类炎症性脂质介质，在固有免疫中发挥作用，但在炎症性疾病中也可能产生病理影响。最近，有人提出白三烯生成与动脉粥样硬化之间存在潜在联系。在冠状动脉和颈动脉粥样硬化斑块中已鉴定出白三烯生物合成酶和白三烯受体的表达，且生物合成酶的水平与不稳定斑块的临床症状相关。5-脂氧合酶途径基因的遗传变异也与发生心肌梗死和中风的相对风险有关。基于这些发现，目前正在评估抗白三烯化合物用于治疗心血管疾病的效果。在动脉粥样硬化的临床前模型中，几种工具化合物已显示可限制病变发展进程，三种化合物，包括两种先前用于治疗哮喘的药物，正在急性冠状动脉综合征患者中进行临床试验。
