Inflammation is thought to play an important role in the pathogenesis of vascular diseases. Lipoprotein‐associated phospholipase A2 (Lp‐PLA2) mediates vascular inflammation through the regulation of lipid metabolism in blood, thus, it has been extensively investigated to identify its role in vascular inflammation‐related diseases, mainly atherosclerosis. Although darapladib, the most advanced Lp‐PLA2 inhibitor, failed to meet the primary endpoints of two large phase III trials in atherosclerosis patients cotreated with standard medical care, the research on Lp‐PLA2 has not been terminated. Novel pathogenic, epidemiologic, genetic, and crystallographic studies regarding Lp‐PLA2 have been reported recently, while novel inhibitors were identified through a fragment‐based lead discovery strategy. More strikingly, recent clinical and preclinical studies revealed that Lp‐PLA2 inhibition showed promising therapeutic effects in diabetic macular edema and Alzheimer's disease. In this review, we not only summarized the knowledge of Lp‐PLA2 established in the past decades but also emphasized new findings in recent years. We hope this review could be valuable for helping researchers acquire a much deeper insight into the nature of Lp‐PLA2, identify more potent and selective Lp‐PLA2 inhibitors, and discover the potential indications of Lp‐PLA2 inhibitors.

中文翻译：

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脂蛋白相关的磷脂酶A2：这个故事还在继续。

人们认为炎症在血管疾病的发病机理中起重要作用。脂蛋白相关的磷脂酶A2（Lp-PLA2）通过调节血液​​中的脂质代谢来介导血管炎症，因此，人们对其进行了广泛的研究，以确定其在与血管炎症相关的疾病（主要是动脉粥样硬化）中的作用。尽管最先进的Lp-PLA2抑制剂darapladib未能达到两项接受标准医学治疗的动脉粥样硬化患者的两项大型III期试验的主要终点，但Lp-PLA2的研究尚未终止。最近已经报道了有关Lp-PLA2的新型致病，流行病学，遗传和晶体学研究，同时通过基于片段的线索发现策略鉴定了新型抑制剂。更惊人的是 最近的临床和临床前研究表明，Lp-PLA2抑制作用在糖尿病性黄斑水肿和阿尔茨海默氏病中显示出可喜的治疗效果。在这篇综述中，我们不仅总结了过去几十年建立的Lp-PLA2的知识，还强调了近年来的新发现。我们希望这篇综述对帮助研究人员更深入地了解Lp‐PLA2的性质，发现更有效和选择性的Lp‐PLA2抑制剂以及发现Lp‐PLA2抑制剂的潜在适应症具有宝贵的价值。