Effect of chronic treatment with acetylsalicylic acid and clopidogrel on atheroprogression and atherothrombosis in ApoE-deficient mice in vivo
Effect of chronic treatment with acetylsalicylic acid and clopidogrel on atheroprogression and atherothrombosis in ApoE-deficient mice in vivo
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DOI：
10.1160/th07-03-0235
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发表时间：
2008-01-01
影响因子：
6.7
通讯作者：
Massberg, Steffen
中科院分区：
文献类型：
--
作者：
Schulz, Christian;Konrad, Ildiko;Massberg, Steffen
乙酰水杨酸（阿萨）和噻吩并吡啶氯吡格雷是公认的抗血小板药物，可显著减少明显动脉粥样硬化患者的继发性心血管事件。然而，它们对动脉粥样硬化病变发展的影响仍然存在争议。将4周龄ApoE缺陷小鼠随机分配至4组，接受胆固醇饮食与阿萨（5 mg/kg）或氯吡格雷（25 mg/kg）或阿萨和氯吡格雷的组合或溶剂，持续8-12周。使用活体显微镜，我们发现，阿萨与氯吡格雷联合每日给药可减少体内动脉粥样硬化斑块破裂后的血小板血栓形成，减少幅度约为50%。然而，阿萨或氯吡格雷单独或联合治疗8-12周，对血小板与功能失调的内皮细胞的粘附或对主动脉根部或颈动脉的动脉粥样硬化病变形成没有显著影响。总之，抗血小板治疗可有效减少体内动脉粥样硬化斑块破裂后的血小板粘附和随后的血栓形成。然而，我们的数据不支持任何一种药物在ApoE缺陷小鼠动脉粥样硬化的一级预防中的作用。
Acetylsalicylic acid (ASA) and the thienopyridine clopidogrel are established anti-platelet drugs that significantly reduce secondary cardiovascular events in patients with manifest atherosclerosis. However, their impact on atherosclerotic lesion development remains controversial. Four-week-old ApoE-deficient mice were randomly assigned to four groups receiving a cholesterol diet together with either ASA (5 mg/kg), or clopidogrel (25 mg/kg), or a combination of both ASA and clopidogrel, or vehicle for 8-12 weeks. Using intravital microscopy we found that daily administration of ASA in combination with clopidogrel reduces platelet thrombus formation following rupture of atherosclerotic plaque in vivo by similar to 50%. However, therapy with ASA or clopidogrel alone, or in combination for a period of 8-12 weeks had no significant effect on adhesion of platelets to dysfunctional endothelial cells or on atherosclerotic lesion formation in the aortic root or the carotid artery. In conclusion, anti-platelet therapy is effective in reducing platelet adhesion and subsequent thrombus formation following rupture of atherosclerotic plaque in vivo. However, our data do not support a role of either drug in the primary prevention of atherosclerosis in ApoE-deficient mice.