Mount Sinai School of Medicine, New York, NY 10029, USA.
Expert Opin Investig Drugs. 2010 Oct;19(10):1245-55. doi: 10.1517/13543784.2010.517193.
The high risk of recurrent cardiovascular events amongst patients with cardiovascular disease receiving evidence-based therapies has prompted investigations into complimentary treatments that may reduce residual risk. Analyses of clinical trials in statin-treated patients demonstrate that elevated lipid levels and an activated systemic inflammatory state are associated with a higher risk of recurrent cardiovascular events.
This article reviews evidence supporting the causal role for secretory phospholipase A(2) (sPLA(2)) in experimental atherosclerosis, the involvement of various sPLA(2) isozymes as mediators of pro-atherogenic lipoprotein remodeling and participants in vascular and systemic inflammatory responses, and the evidence that sPLA(2) inhibition reduces atherosclerosis in experimental models and biomarkers associated with cardiovascular events in coronary heart disease (CHD) patients.
The experimental basis for sPLA(2) inhibition with varespladib methyl as a potential candidate for lowering recurrent cardiovascular events particularly in acute coronary syndrome patients is discussed.
Varespladib methyl therapy reduces atherogenic lipoprotein concentrations and systemic inflammatory markers in CHD patients. The future role of varespladib methyl in CHD patients awaits the results of ongoing clinical trials.
心血管疾病患者接受循证治疗后，心血管事件再次发生的风险较高，这促使人们研究可能降低残余风险的补充治疗方法。对他汀类药物治疗患者的临床试验分析表明，血脂水平升高和全身炎症状态激活与心血管事件再次发生的风险增加相关。
本文综述了支持分泌型磷脂酶 A2（sPLA2）在实验性动脉粥样硬化中起因果作用的证据，涉及各种 sPLA2 同工酶作为促动脉粥样硬化脂蛋白重塑的介质以及参与血管和全身炎症反应的介质，以及 sPLA2 抑制可减少实验模型中动脉粥样硬化和冠心病（CHD）患者心血管事件相关生物标志物的证据。
讨论了 varespladib 甲基抑制 sPLA2 的实验基础，varespladib 甲基可能是降低心血管事件再次发生风险的候选药物，特别是在急性冠状动脉综合征患者中。varespladib 甲基在 CHD 患者中的未来作用有待正在进行的临床试验结果揭晓。
