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

Steven R Lentz; Francis J Miller; Donald J Piegors; Rochelle A Erger; José A Fernández; John H Griffin; Donald D Heistad

doi:10.1161/01.CIR.0000024982.11646.25

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

Journal article

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

Steven R Lentz, Francis J Miller, Donald J Piegors, Rochelle A Erger, José A Fernández, John H Griffin and Donald D Heistad

Circulation (New York, N.Y.), Vol.106(7), pp.842-846

08/13/2002

DOI: 10.1161/01.CIR.0000024982.11646.25

PMID: 12176958

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Abstract

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.

Details

Title: Subtitle: Anticoagulant Responses to Thrombin Are Enhanced During Regression of Atherosclerosis in Monkeys
Creators: Steven R Lentz - From the Veterans Affairs Medical Center (S.R.L., R.A.E., D.D.H.) and Departments of Internal Medicine (S.R.L., F.J.M., D.J.P., D.D.H.) and Pharmacology (D.D.H.), University of Iowa College of Medicine, Iowa City, Iowa, and The Scripps Research Institute (J.A.F., J.H.G.), La Jolla, Calif
Francis J Miller - From the Veterans Affairs Medical Center (S.R.L., R.A.E., D.D.H.) and Departments of Internal Medicine (S.R.L., F.J.M., D.J.P., D.D.H.) and Pharmacology (D.D.H.), University of Iowa College of Medicine, Iowa City, Iowa, and The Scripps Research Institute (J.A.F., J.H.G.), La Jolla, Calif
Donald J Piegors - From the Veterans Affairs Medical Center (S.R.L., R.A.E., D.D.H.) and Departments of Internal Medicine (S.R.L., F.J.M., D.J.P., D.D.H.) and Pharmacology (D.D.H.), University of Iowa College of Medicine, Iowa City, Iowa, and The Scripps Research Institute (J.A.F., J.H.G.), La Jolla, Calif
Rochelle A Erger - From the Veterans Affairs Medical Center (S.R.L., R.A.E., D.D.H.) and Departments of Internal Medicine (S.R.L., F.J.M., D.J.P., D.D.H.) and Pharmacology (D.D.H.), University of Iowa College of Medicine, Iowa City, Iowa, and The Scripps Research Institute (J.A.F., J.H.G.), La Jolla, Calif
José A Fernández - From the Veterans Affairs Medical Center (S.R.L., R.A.E., D.D.H.) and Departments of Internal Medicine (S.R.L., F.J.M., D.J.P., D.D.H.) and Pharmacology (D.D.H.), University of Iowa College of Medicine, Iowa City, Iowa, and The Scripps Research Institute (J.A.F., J.H.G.), La Jolla, Calif
John H Griffin - From the Veterans Affairs Medical Center (S.R.L., R.A.E., D.D.H.) and Departments of Internal Medicine (S.R.L., F.J.M., D.J.P., D.D.H.) and Pharmacology (D.D.H.), University of Iowa College of Medicine, Iowa City, Iowa, and The Scripps Research Institute (J.A.F., J.H.G.), La Jolla, Calif
Donald D Heistad - From the Veterans Affairs Medical Center (S.R.L., R.A.E., D.D.H.) and Departments of Internal Medicine (S.R.L., F.J.M., D.J.P., D.D.H.) and Pharmacology (D.D.H.), University of Iowa College of Medicine, Iowa City, Iowa, and The Scripps Research Institute (J.A.F., J.H.G.), La Jolla, Calif
Resource Type: Journal article
Publication Details: Circulation (New York, N.Y.), Vol.106(7), pp.842-846
DOI: 10.1161/01.CIR.0000024982.11646.25
PMID: 12176958
NLM abbreviation: Circulation
ISSN: 0009-7322
eISSN: 1524-4539
Publisher: Lippincott Williams & Wilkins
Language: English
Date published: 08/13/2002
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040480502771

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