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.


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.
Lentz
Steven R
SR
Veterans Affairs Medical Center, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA. steven-lentz@uiowa.edu
Miller
Francis J
FJ
Piegors
Donald J
DJ
Erger
Rochelle A
RA
Fernández
José A
JA
Griffin
John H
JH
Heistad
Donald D
DD
D000818:Animals; D000925:Anticoagulants / Q000097:blood*; D001161:Arteriosclerosis / Q000097:blood*; D001777:Blood Coagulation / Q000187:drug effects*; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D004036:Diet, Atherogenic; D018752:Diet, Fat-Restricted; D005263:Femoral Artery / Q000187:drug effects / Q000473:pathology; D006487:Hemostasis / Q000187:drug effects*; D006710:Homocysteine / Q000097:blood; D007262:Infusions, Intravenous; D008055:Lipids / Q000097:blood; D008168:Lung / Q000378:metabolism; D008252:Macaca fascicularis; D010314:Partial Thromboplastin Time; D011486:Protein C / Q000378:metabolism; D012075:Remission, Spontaneous; D013917:Thrombin / Q000494:pharmacology*; D018180:Thrombomodulin / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D000925:Anticoagulants; D008055:Lipids; D011486:Protein C; D018180:Thrombomodulin; D014665:Vasodilator Agents; D006710:Homocysteine; D002784:Cholesterol; D013917:Thrombin