脂蛋白相关性磷脂酶A_2:一种新型的、具有前景的评估心血管危险的生化标记物

Lipoprotein-associated phospholipase A_2:a novel and promising biochemical marker for evaluating cardiovascular risk

动脉粥样硬化及其相关的心血管疾病的发病率和死亡率至今仍居全球首位。尽管加强了干预措施,但心血管残余风险仍相当高。脂蛋白相关性磷脂酶A2(Lp-PLA2)是一种新型的、独立的血管炎症特异性和动脉粥样硬化特异性生化标记物。大量科学和临床研究证实,Lp-PLA2具有促动脉粥样硬化作用,并与心血管事件的发生呈正相关。目前,根据成年治疗小组Ⅲ(ATPⅢ)指南,推荐Lp-PLA2作为传统危险因子的辅助指标,从而可以优化对未来心血管风险的评估。令人鼓舞的是,一种口服的Lp-PLA2特异性抑制剂(Darapladib),其基础研究和临床前期试验取得了显著的成果。同时,有两项正在进行的针对Darapladib的III期临床试验,以评估其改善心血管结局的疗效和安全性。此外,对于中高危的人群,Lp-PLA2对指导危险分层、建立治疗方案和预后评估具有潜在的价值。该文将对Lp-PLA2的生化特性、在动脉粥样硬化中的作用及其在科学和临床研究的结果作出归纳总结。

Atherosclerosis and its associated cardiovascular diseases （CVD）are still the leading cause of morbidity and mortality worldwide. Although intensified interventions have been applied,the residual cardiovascular（CV）risks are still very high. Lipoprotein-associated phospholipase A2 （Lp-PLA2 ）is a novel and unique biomarker highly specific for vascular inflammation and atherosclerosis. A large number of basic and clinical studies have demonstrated that Lp-PLA2 is pro-atherogenic and correlates positively with CV events.Currently,in the Adult Treatment Panel III （ATP III）guideline,Lp-PLA2 is recommended as an adjunct to traditional risk factors in assessing the potential CV risks. Encouragingly,darapladib,a specific and orally ac-tive inhibitor of Lp-PLA2 ,has been tested both in basic research and preclinical trials and the outcomes are quite striking. Additionally,there are two phase III clinical trials ongoing to evaluate the efficacy and safety of darapladib on cardiovascular outcomes. With regard to the potential values of Lp-PLA2 in risk stratification, therapeutic regimen establishment and prognosis evaluation in patients with moderate or high risk,this review is to summarize the relevant data about the bio-chemical characteristics of Lp-PLA2 ,the actions of Lp-PLA2 on atherosclerosis and the results of Lp-PLA2 in scientific research and clinical studies.