Enhanced thrombin generation and platelet binding on herpes simplex virus-infected endothelium.
- 1 November 1988
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 85 (21), 8227-8230
- https://doi.org/10.1073/pnas.85.21.8227
Abstract
Atherosclerotic lesions have been reported to contain herpes simplex virus 1 (HSV-1) genomic material. This, and other previous evidence, suggests that latent viral infection may be an atherogenic trigger. Moreover, active HSV-1 lesions manifest marked fibrin deposition in microvessels. In this report we show that very early infection of human endothelial cells with HSV-1 appears to alter surface conformation as detected by merocyanine 540 staining. Concomitantly, the efficiency of prothrombinase complex assembly increases, resulting in a 2- to 3-fold accelerated rate of thrombin generation on the cell surface. Increased thrombin generation is probably doubly procoagulant, since we also demonstrate that thrombin-induced platelet accumulation on HSV-infected endothelium (50.7 +/- 9.3%) is increased compared to uninfected endothelium (9.5 +/- 2.1%; P less than 0.002). Associated with HSV infection, prostacyclin secretion in response to thrombin is diminished by a factor of 20, probably explaining the enhanced platelet attachment. We conclude that HSV infection shifts endothelial cell properties from anticoagulant to procoagulant, both by promoting prothrombinase complex formation and function and by increasing platelet binding, well before cell disruption takes place. Virus-induced changes in the endothelial plasma membrane and diminished prostacyclin secretion are suggested as the pathways for this pathophysiologic mechanism, which may be germane to atherosclerotic thrombosis as well as HSV-mediated tissue necrosis.Keywords
This publication has 23 references indexed in Scilit:
- Herpes simplex virus type 1 infection of endothelium reduces collagen and fibronectin synthesis.1985
- Human prothrombinase complex assembly and function on isolated peripheral blood cell populations.Online Journal of Public Health Informatics, 1985
- Interaction between enteroviruses and human endothelial cells in vitro. Alterations in the physical properties of endothelial cell plasma membrane and adhesion of human granulocytes.1985
- Replication of Human Cytomegalovirus in Endothelial CellsThe Journal of Infectious Diseases, 1984
- Coagulation factor Va binds to human umbilical vein endothelial cells and accelerates protein C activation.JCI Insight, 1984
- Natural anticoagulant mechanisms.JCI Insight, 1984
- Perturbations of the endothelium.1984
- Viruses in the etiology of atherosclerosis.Proceedings of the National Academy of Sciences of the United States of America, 1983
- Synthesis of Antihemophilic Factor Antigen by Cultured Human Endothelial CellsJCI Insight, 1973
- PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENTOnline Journal of Public Health Informatics, 1951