Anticoagulant responses to thrombin are enhanced during regression of atherosclerosis in monkeys.
Anticoagulant responses to thrombin are enhanced during regression of atherosclerosis in monkeys.
复制标题
在猴子动脉粥样硬化消退过程中，对凝血酶的抗凝反应增强。
DOI：
10.1161/01.cir.0000024982.11646.25
复制
发表时间：
2002
期刊：
影响因子：
37.8
通讯作者：
Heistad,DonaldD
中科院分区：
文献类型：
--
作者：
Lentz,StevenR;MillerJr,FrancisJ;Piegors,DonaldJ;Erger,RochelleA;Fernández,JoséA;Griffin,JohnH;Heistad,DonaldD
饮食诱导的猴动脉粥样硬化对凝血酶产生异常的抗凝反应，包括活化蛋白C（APC）的生成减少。我们测试的假设，即凝血酶抗凝反应增加回归正常的atherosclerosis.Methods和Results-Six食蟹猴喂养高脂致动脉粥样硬化饮食44个月，然后低脂肪回归饮食8个月。回归饮食后，血清总胆固醇从417±44降至68±6 mg/dL（平均值±SEM），LDL胆固醇从375±44降至27±5 mg/dL。作为对凝血酶输注的响应，活化部分凝血活酶时间（APTT）在回归饮食之前增加了11±3秒，在回归饮食之后增加了41±22秒（P=0.01）。循环血浆APC峰值水平在回归饮食前为52±9 ng/mL，回归饮食后为88±17 ng/mL（P=0.01）。血浆因子V的APC敏感性在回归饮食之前和之后是相同的。三个额外的动脉粥样硬化的猴子，保持在高脂肪饮食8个月表现出没有变化的APTT或蛋白C的活化在响应thrombosis. Conclusions短期饮食退化的动脉粥样硬化产生增强的抗凝反应凝血酶在体内。
Background—Diet-induced atherosclerosis in monkeys produces abnormal anticoagulant responses to thrombin, including decreased generation of activated protein C (APC). We tested the hypothesis that anticoagulant responses to thrombin increase toward normal during regression of atherosclerosis.Methods and Results—Six cynomolgus monkeys were fed a high-fat atherogenic diet for 44 months and then a low-fat regression diet for 8 months. Serum total cholesterol decreased from 417±44 to 68±6 mg/dL (mean±SEM) and LDL cholesterol decreased from 375±44 to 27±5 mg/dL after the regression diet. In response to infusion of thrombin, the activated partial thromboplastin time (APTT) increased by 11±3 seconds before the regression diet and by 41±22 seconds after the regression diet (P=0.01). The peak level of circulating plasma APC was 52±9 ng/mL before the regression diet and 88±17 ng/mL after the regression diet (P=0.01). The APC sensitivity of plasma factor V was identical before and after the regression diet. Three additional atherosclerotic monkeys that remained on the high-fat diet for 8 months demonstrated no change in APTT or activation of protein C in response to thrombin.Conclusions—Short-term dietary regression of atherosclerosis produces enhanced anticoagulant responses to thrombin in vivo.