The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
Inhibition of thrombomodulin surface expression and protein C activation by the thrombogenic agent homocysteine.
Open accessAbstract
Elevated levels of plasma homocysteine are associated with both venous and arterial thrombosis. Homocysteine inhibits the function of thrombomodulin, an anticoagulant glycoprotein on the endothelial surface that serves as a cofactor for the activation of protein C by thrombin. The effects of homocysteine on thrombomodulin expression and protein C activation were investigated in cultured human umbilical vein endothelial cells and CV-1(18A) cells that express recombinant human thrombomodulin. Addition of 5 mM homocysteine to endothelial cells produced slight increases in thrombomodulin mRNA and thrombomodulin synthesis without affecting cell viability. In both cell types, thrombomodulin synthesized in the presence of homocysteine remained sensitive to digestion with endoglycosidase H and failed to appear on the cell surface, suggesting impaired transit along the secretory pathway. In a cell-free protein C activation assay, homocysteine irreversibly inactivated both thrombomodulin and protein C in a process that required free thiol groups and was inhibited by the oxidizing agents diamide or N-ethylmaleimide. By inhibiting both thrombomodulin surface expression and protein C activation, homocysteine may contribute to the development of thrombosis in patients with cystathionine beta-synthase deficiency.
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Cites
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Cited by
Homocysteine and Cardiovascular Disease
Refsum, H., Ueland, P. M., Nygård, O., & Vollset, S. E. (1998) · Annual Review of Medicine · doi:10.1146/annurev.med.49.1.31 · Cited by 2,180
Homocysteine and Atherothrombosis
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Homocyst(e)ine Decreases Bioavailable Nitric Oxide by a Mechanism Involving Glutathione Peroxidase
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Platelet activation in type 2 diabetes mellitus
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Metadata
- Authors
- Lentz, S. R., & Sadler, J. E.
- Venue
- Journal of Clinical Investigation
- Published
- 1991-12-01
- Volume
- 88
- Issue
- 6
- Pages
- 1906-1914
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2040900375
- Cited by
- 448
- References
- 38
- FWCI
- 5.74
- Type
- journal article
- Language
- en
- Open access
- bronze
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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