Journal article
Effect of hyperhomocysteinemia on protein C activation and activity
Blood, Vol.100(6), pp.2108-2112
2002
DOI: 10.1182/blood-2002-03-0727
PMID: 12200374
Abstract
Hyperhomocysteinemia has been proposed to inhibit the protein C anticoagulant system through 2 mechanisms: decreased generation of activated protein C (APC) by thrombin, and resistance to APC caused by decreased inactivation of factor Va (FVa). We tested the hypotheses that generation of APC by thrombin is impaired in hyperhomocysteinemia in monkeys and that hyperhomocysteinemia produces resistance to APC in monkeys, mice, and humans. In a randomized crossover study, cynomolgus monkeys were fed either a control diet or a hyperhomocysteinemic diet for 4 weeks. Plasma total homocysteine (tHcy) was approximately 2-fold higher when monkeys were on the hyperhomocysteinemic diet than when they were on the control diet (9.8 +/- 2.0 microM versus 5.6 +/- 1.0 microM; P <.05). After infusion of human thrombin (25 microg/kg of body weight), the peak level of plasma APC was 136 +/- 16 U/mL in monkeys fed the control diet and 127 +/- 13 U/mL in monkeys fed the hyperhomocysteinemic diet (P >.05). The activated partial thromboplastin time was prolonged to a similar extent by infusion of thrombin in monkeys fed the control diet and in those fed the hyperhomocysteinemic diet. The sensitivity of plasma FV to human APC was identical in monkeys on control diet and those on hyperhomocysteinemic diet. We also did not detect resistance of plasma FV to APC in hyperhomocysteinemic mice deficient in cystathionine beta-synthase (plasma tHcy, 93 +/- 16 microM) or in human volunteers with acute hyperhomocysteinemia (plasma tHcy, 45 +/- 6 microM). Our findings indicate that activation of protein C by thrombin and inactivation of plasma FVa by APC are not impaired during moderate hyperhomocysteinemia in vivo.
Details
- Title: Subtitle
- Effect of hyperhomocysteinemia on protein C activation and activity
- Creators
- Steven R LENTZ - Baylor Institute of Metabolic Disease, Dallas, TX, United StatesDonald J PIEGORS - Baylor Institute of Metabolic Disease, Dallas, TX, United StatesJosé A FERNANDEZ - Baylor Institute of Metabolic Disease, Dallas, TX, United StatesRochelle A ERGER - Baylor Institute of Metabolic Disease, Dallas, TX, United StatesErland ARNING - Baylor Institute of Metabolic Disease, Dallas, TX, United StatesM. René MALINOW - Baylor Institute of Metabolic Disease, Dallas, TX, United StatesJohn H GRIFFIN - Baylor Institute of Metabolic Disease, Dallas, TX, United StatesTeodoro BOTTIGLIERI - Baylor Institute of Metabolic Disease, Dallas, TX, United StatesWilliam G HAYNES - Baylor Institute of Metabolic Disease, Dallas, TX, United StatesDonald D HEISTAD - Baylor Institute of Metabolic Disease, Dallas, TX, United States
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.100(6), pp.2108-2112
- Publisher
- The Americain Society of Hematology; Washington, DC
- DOI
- 10.1182/blood-2002-03-0727
- PMID
- 12200374
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Language
- English
- Date published
- 2002
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040013502771
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