Document Detail


Impaired anticoagulant response to infusion of thrombin in atherosclerotic monkeys associated with acquired defects in the protein C system.
MedLine Citation:
PMID:  10397693     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
S R Lentz; J A Fernández; J H Griffin; D J Piegors; R A Erger; M R Malinow; D D Heistad
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  19     ISSN:  1079-5642     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  1999 Jul 
Date Detail:
Created Date:  1999-07-29     Completed Date:  1999-07-29     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1744-50     Citation Subset:  IM    
Affiliation:
Veterans Affairs Medical Center, Departments of Internal Medicine and Pharmacology, University of Iowa College of Medicine, Iowa City, Iowa, USA. steven-lentz@uiowa.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Anticoagulants / pharmacology*
Arteriosclerosis / blood*
Cholesterol / blood
Homocysteine / blood
Macaca fascicularis
Partial Thromboplastin Time
Protein C / analysis,  physiology*
Thrombin / pharmacology*
Vitamin B Complex / pharmacology
Grant Support
ID/Acronym/Agency:
HL-14388/HL/NHLBI NIH HHS; HL-16066/HL/NHLBI NIH HHS; HL-21544/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Anticoagulants; 0/Protein C; 12001-76-2/Vitamin B Complex; 454-28-4/Homocysteine; 57-88-5/Cholesterol; EC 3.4.21.5/Thrombin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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