Journal article
Impaired Anticoagulant Response to Infusion of Thrombin in Atherosclerotic Monkeys Associated With Acquired Defects in the Protein C System
Arteriosclerosis, thrombosis, and vascular biology, Vol.19(7), pp.1744-1750
07/1999
DOI: 10.1161/01.ATV.19.7.1744
PMID: 10397693
Abstract
To examine the effects of atherosclerosis on the protein C anticoagulant pathway in vivo, we measured anticoagulant responses to intravenous administration of human alpha-thrombin or activated protein C (APC) in cynomolgus monkeys. Two groups of monkeys were fed either a control diet (n=18) or an atherogenic diet (n=12) that produces both hypercholesterolemia and moderate hyperhomocyst(e)inemia. A third group (n=8) was fed an atherogenic diet for 15 months, and then fed the atherogenic diet supplemented with B vitamins for 6 months to correct the hyperhomocyst(e)inemia. The plasma homocyst(e)ine level was higher in monkeys fed the atherogenic diet (9.6+/-1.0 micromol/L) than in monkeys fed the control diet (3.7+/-0.2 micromol/L) or the atherogenic diet with B vitamins (3.6+/-0.2 micromol/L) (P<0.001). Infusion of thrombin produced a much greater prolongation of the activated partial thromboplastin time in monkeys fed the control diet (52+/-10 seconds) than in monkeys fed the atherogenic diet either with (24+/-4 seconds) or without (27+/-5 seconds) supplemental B vitamins (P<0.02). Thrombin-dependent generation of circulating APC was higher in control (294+/-17 U/mL) than in atherosclerotic (240+/-14 U/mL) monkeys (P<0.05), although levels of fibrinogen, plasminogen, D-dimer, and thrombin-antithrombin complexes were similar in each group. Injection of human APC produced a similar prolongation of the activated partial thromboplastin time in control (31+/-3 seconds) and atherosclerotic (29+/-2 seconds) monkeys. These findings provide evidence for impaired anticoagulation, due partly to decreased formation of APC, in atherosclerosis. The blunted anticoagulant response to thrombin in hypercholesterolemic monkeys was not corrected by supplementation with B vitamins.
Details
- Title: Subtitle
- Impaired Anticoagulant Response to Infusion of Thrombin in Atherosclerotic Monkeys Associated With Acquired Defects in the Protein C System
- Creators
- Steven R Lentz - From the Veterans Affairs Medical Center (S.R.L., R.A.E., D.D.H.), and the Departments of Internal Medicine (S.R.L., D.J.P., D.D.H.) and Pharmacology (D.D.H.), University of Iowa College of Medicine, Iowa City, Iowa; The Scripps Research Institute (J.A.F., J.H.G.), La Jolla, Calif; and the Oregon Regional Primate Research Center (M.R.M.), Beaverton, OreJosé A Fernández - From the Veterans Affairs Medical Center (S.R.L., R.A.E., D.D.H.), and the Departments of Internal Medicine (S.R.L., D.J.P., D.D.H.) and Pharmacology (D.D.H.), University of Iowa College of Medicine, Iowa City, Iowa; The Scripps Research Institute (J.A.F., J.H.G.), La Jolla, Calif; and the Oregon Regional Primate Research Center (M.R.M.), Beaverton, OreJohn H Griffin - From the Veterans Affairs Medical Center (S.R.L., R.A.E., D.D.H.), and the Departments of Internal Medicine (S.R.L., D.J.P., D.D.H.) and Pharmacology (D.D.H.), University of Iowa College of Medicine, Iowa City, Iowa; The Scripps Research Institute (J.A.F., J.H.G.), La Jolla, Calif; and the Oregon Regional Primate Research Center (M.R.M.), Beaverton, OreDonald J Piegors - From the Veterans Affairs Medical Center (S.R.L., R.A.E., D.D.H.), and the Departments of Internal Medicine (S.R.L., D.J.P., D.D.H.) and Pharmacology (D.D.H.), University of Iowa College of Medicine, Iowa City, Iowa; The Scripps Research Institute (J.A.F., J.H.G.), La Jolla, Calif; and the Oregon Regional Primate Research Center (M.R.M.), Beaverton, OreRochelle A Erger - From the Veterans Affairs Medical Center (S.R.L., R.A.E., D.D.H.), and the Departments of Internal Medicine (S.R.L., D.J.P., D.D.H.) and Pharmacology (D.D.H.), University of Iowa College of Medicine, Iowa City, Iowa; The Scripps Research Institute (J.A.F., J.H.G.), La Jolla, Calif; and the Oregon Regional Primate Research Center (M.R.M.), Beaverton, OreM. René Malinow - From the Veterans Affairs Medical Center (S.R.L., R.A.E., D.D.H.), and the Departments of Internal Medicine (S.R.L., D.J.P., D.D.H.) and Pharmacology (D.D.H.), University of Iowa College of Medicine, Iowa City, Iowa; The Scripps Research Institute (J.A.F., J.H.G.), La Jolla, Calif; and the Oregon Regional Primate Research Center (M.R.M.), Beaverton, OreDonald D Heistad - From the Veterans Affairs Medical Center (S.R.L., R.A.E., D.D.H.), and the Departments of Internal Medicine (S.R.L., D.J.P., D.D.H.) and Pharmacology (D.D.H.), University of Iowa College of Medicine, Iowa City, Iowa; The Scripps Research Institute (J.A.F., J.H.G.), La Jolla, Calif; and the Oregon Regional Primate Research Center (M.R.M.), Beaverton, Ore
- Resource Type
- Journal article
- Publication Details
- Arteriosclerosis, thrombosis, and vascular biology, Vol.19(7), pp.1744-1750
- DOI
- 10.1161/01.ATV.19.7.1744
- PMID
- 10397693
- NLM abbreviation
- Arterioscler Thromb Vasc Biol
- ISSN
- 1079-5642
- eISSN
- 1524-4636
- Language
- English
- Date published
- 07/1999
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040353002771
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