Induction of endothelial cell procoagulant activity by cytomegalovirus infection

Dam-Mieras, M.C.E. van; Bruggeman, G.A.; Muller, A.D.; Debie, Wiel H.; Zwaal, R.F.A.

doi:10.1016/0049-3848(87)90241-6

Cited by 82 publications

(36 citation statements)

References 17 publications

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“…This has led to the hypothesis that latent herpes infections of vascularwall cells may be atherogenic (13). Our findings that HSV infection promotes prothrombotic phenomena in human endothelium, and a report (27) that rat endothelial 'cell infection with a herpesvirus, rat cytomegalovirus, shortens the clotting time on the surface of these cells, prompt this construct: herpes infection not only damages endothelium as an initiating event in atherosclerotic plaque formation but promotes thrombosis on these lesions as well.…”

Section: Discussionmentioning

confidence: 65%

Enhanced thrombin generation and platelet binding on herpes simplex virus-infected endothelium.

Visser

Tracy

Vercellotti

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

126

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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 endothellum (50.7 ± 9.3%) is increased compared to uninfected endothelium (9.5 ± 2.1%; P < 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 endothellal 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.An intact vascular endothelium is actively antithrombotic. Rather than forming a passive vascular lining, endothelium has a variety of natural anticoagulant properties that are able to exert a dampening effect upon the coagulation cascade (1, 2): heparin-like species, thrombomodulin, plasminogen activator, and prostacyclin are endothelial constituents thought to contribute to vascular thromboresistance. Consequently, a breach of this barrier by mechanical disruption of the endothelial lining with frank endothelial loss and exposure of the subendothelium can lead to massive coagulation activation and platelet adherence. More subtle injury to endothehum that might alter its thromboresistant properties has only recently emerged as a topic of inquiry (3). Theoretically, several different mechanisms may be involved in diminished endothelial thromboresistance: (i) decreased production or exhibition of the above-mentioned antithrombotic factors; (ii) increased production or secretion ofthrombogenic factors such as tissue factor, platelet-activating factor, von Willebrand factor, and plasminogen-activator inhibitor; and (iii) changes in the endothelial cell surface, leading to altered exposure of proteins or procoagulant phospholipids.With regard to mechanism iii, endothelial cell surface alterations can result from viral infection, which readily occurs with several viruses in vitro. Diverse viruses replicate readily in cultured endothelium, including herpesviruses, adenoviruses, and enteroviruses, among others (4,...

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Section: Discussionmentioning

confidence: 65%

Enhanced thrombin generation and platelet binding on herpes simplex virus-infected endothelium.

Visser

Tracy

Vercellotti

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

126

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“…Although we were able to confirm that HSV-1 induced tissue factor, it was a far less potent stimulus than measles virus. This effect was not seen with CMV, although CMV has been reported to induce PCA in rat aortic endothelium (Van Dam-Mieras et al, 1987), suggesting that PCA-inducing capacity is related to the nature of the virus, rather than a phenomenon associated with viral infection in general. It is possible that cytokines present in the viral inocula contributed to PCA induction by measles virus.…”

Section: Discussionmentioning

confidence: 75%

Measles Virus Induction of Human Endothelial Cell Tissue Factor Procoagulant Activity in Vitro

Mazure

Grundy

Nygård

et al. 1994

Journal of General Virology

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“…57 It has been shown that tunicamycin, which hinders glycosylation, abolishes HSV-1-and CMV-induced adherence of MCs and PMNs, indicating that glycoproteins induced by virus infection have a role in PMN and MC adherence. 56 In 1987, Van Dam Mieras et al 58 showed an association between CMV infection and a hypercoagulant state. More recently, HSV has also been implicated in leading to a procoagulant state.…”

Section: Infectionsmentioning

confidence: 99%

Hepatic artery thrombosis after orthotopic liver transplantation: A review of nonsurgical causes

et al. 2001

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Induction of endothelial cell procoagulant activity by cytomegalovirus infection

Cited by 82 publications

References 17 publications

Enhanced thrombin generation and platelet binding on herpes simplex virus-infected endothelium.

Enhanced thrombin generation and platelet binding on herpes simplex virus-infected endothelium.

Measles Virus Induction of Human Endothelial Cell Tissue Factor Procoagulant Activity in Vitro

Hepatic artery thrombosis after orthotopic liver transplantation: A review of nonsurgical causes

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