Anticoagulant Responses to Thrombin Are Enhanced During Regression of Atherosclerosis in Monkeys

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...