Effect of hyperhomocysteinemia on protein C activation and activity
| Autor: | Donald D. Heistad, John H. Griffin, William G. Haynes, Erland Arning, M. Rene Malinow, José A. Fernández, Steven R. Lentz, Rochelle A. Erger, Teodoro Bottiglieri, Donald J. Piegors |
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| Rok vydání: | 2002 |
| Předmět: |
Male
medicine.medical_specialty Hyperhomocysteinemia Immunology Cystathionine beta-Synthase Biology Biochemistry chemistry.chemical_compound Mice Thrombin Methionine In vivo Internal medicine medicine Animals Humans medicine.diagnostic_test Factor V Cell Biology Hematology Haplorhini medicine.disease Cystathionine beta synthase Enzyme Activation Mice Inbred C57BL Disease Models Animal Endocrinology chemistry biology.protein Female Partial Thromboplastin Time Protein C medicine.drug Partial thromboplastin time |
| Zdroj: | Blood. 100(6) |
| ISSN: | 0006-4971 |
| Popis: | 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 μM versus 5.6 ± 1.0 μM; 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 β-synthase (plasma tHcy, 93 ± 16 μM) or in human volunteers with acute hyperhomocysteinemia (plasma tHcy, 45 ± 6 μM). 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. |
| Databáze: | OpenAIRE |
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