白三烯在动脉粥样硬化形成及治疗中的作用

Roles of leukotriene in pathogenesis and treatment of atherosclerosis

动脉粥样硬化(atherosclerosis,AS)是常见的心血管疾病,能引起严重的并发症,是导致病人死亡最常见的病因之一。炎症反应是动脉粥样硬化的发病机制之一,而白三烯(leukotrienes,LTs)是重要的炎症介质,在炎症信号通路中具有免疫调节和促炎作用。白三烯与动脉粥样硬化密切相关。白三烯的产生主要通过5-脂氧合酶和环氧合酶产生。白三烯B4(leukotrienes B4,LTB4)、半胱氨酸-白三烯(cysteinyl leukotrienes,CysLTs)等通过诱导中性粒细胞聚集,增强内皮细胞通透性,介导血管平滑肌细胞核钙信号转导,促进动脉粥样硬化的形成。一些与动脉粥样硬化有关的疾病,如阻塞性睡眠呼吸暂停的夜间间歇性低氧显著增加了白三烯B4的产生及5-脂氧合酶(5-lipoxygenase,5-LOX)的表达;糖尿病患者基质金属蛋白酶明显增加,可促进5-脂氧合酶和白三烯B4表达。本文论述了白三烯及其代谢途径中相关物质、产生白三烯相关疾病与动脉粥样硬化的关系,提出了抑制白三烯受体、5-脂氧合酶途径和白三烯A4水解酶等新的治疗动脉粥样硬化的策略。

Atherosclerosis(AS) is a common cardiovascular disease that can cause serious complications and is one of the most common causes of patient death. The inflammatory response is involved in the pathogenesis of atherosclerosis and leukotrienes(LTs) are important inflammatory mediators that play immunomodulatory and proinflammatory roles in the inflammatory signaling pathway. Leukotrienes are closely related to atherosclerosis. Leukotriene B4(LTB4), cysteinyl leukotrienes, and the 5-lipoxygenase(5-LOX) pathway trigger a plaque formation disorder that promotes AS by inducing neutrophil aggregation, enhancing endothelial cell permeability, and mediating nuclear calcium signal transduction in vascular smooth muscle. Additionally, obstructive sleep apnea(OSA) and diabetes that produce LTs are associated with AS. Intermittent hypoxia in patients with OSA increases production of LTB4 and expression of 5-lipoxygenase. Increased matrix metalloproteases in diabetic patients promote expression of 5-LOX and LTB4. This article discussed the current research on the roles of LTs and related substances in the metabolic pathway in the pathogenesis of atherosclerosis and its treatment. Thus, some new treatment strategies aimed at LTs for anti-AS effects have been proposed, which include inhibition of LT receptors, the 5-LOX pathway and LTA4 hydrolytic enzyme.