Acute rejection before cytomegalovirus infection enhances von Willebrand factor and soluble VCAM-1 in blood

Kas-Deelen, A.M.; Harmsen, Martin C.; Maar, Eltjo F. de; Oost-Kort, Wia W.; Tervaert, Jan Willem Cohen; Meer, Jan van der; Son, Willem J. van; The, T. H.

doi:10.1046/j.1523-1755.2000.00438.x

Cited by 28 publications

(16 citation statements)

References 39 publications

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“…Furthermore, cells infected with Towne secreted significantly higher levels of soluble vWF than uninfected cells, is in accordance with the findings of Bruggeman et al, who reported reduced expression of vWF in AD169-infected cells (3). Our findings are also supported by the observation in vivo that the level of vWF in plasma has been shown to be increased during HCMV infection in kidneys (13).…”

Section: Discussionsupporting

confidence: 89%

Human Cytomegalovirus Infection of Endothelial Cells Triggers Platelet Adhesion and Aggregation

Rahbar

Söderberg‐Nauclér²

2005

J Virol

106

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Human cytomegalovirus (HCMV) is an opportunistic pathogen that has been implicated in the pathogenesis of vascular diseases. HCMV infection of endothelial cells may lead to vascular damage in vitro, and acutephase HCMV infection has been associated with thrombosis. We hypothesized that viral infection of endothelial cells activates coagulation cascades and contributes to thrombus formation and acute vascular catastrophes in patients with atherosclerotic disease. To assess the effects of HCMV on thrombogenesis, we examined the adhesion and aggregation of blood platelets to uninfected and HCMV-infected endothelial cells. At 7 days after infection, platelet adherence and aggregation were greater in infected than in uninfected cultures (2,000 platelets/100 cells and 225 ؎ 15 [mean ؎ standard error of the mean] aggregates/five microscopic fields versus 100 platelets/100 cells and no aggregates). von Willebrand factor (vWF), ICAM-1, and VCAM-1 but not collagen IV, E-selectin, P-selectin, CD13, and CD31 were expressed at higher levels on infected cells than on uninfected cells. Platelet aggregation was inhibited by blocking of platelet GPIb (with blocking antibodies) or GPIIb/IIIa (with ReoPro) or by blocking of vWF (with polyclonal antibodies to vWF). Furthermore, blocking of vWF, platelet GPIb, and ICAM-1 but not of the endothelial cell marker CD13, ␣ 5 ␤ 3 -integrin, or HCMV glycoprotein B reduced platelet adherence to infected cells by 75% ؎ 5%, 74% ؎ 5%, or 18% ؎ 5%, respectively. The increased thrombogenicity was dependent on active virus replication and could be inhibited by foscarnet and ganciclovir; these results suggest that a late viral gene may be mediating this phenomenon, which may contribute to vascular catastrophes in patients with atherosclerotic disease.

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Section: Discussionsupporting

confidence: 89%

Human Cytomegalovirus Infection of Endothelial Cells Triggers Platelet Adhesion and Aggregation

Rahbar

Söderberg‐Nauclér²

2005

J Virol

106

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“…We have previously demonstrated the presence of cytomegalic (CMV‐infected) endothelial cells (CEC) and non‐CMV infected endothelial cells (EC) in the blood of renal transplant recipients with CMV infection (26). Furthermore, we showed increased levels of Von Willebrand Factor (VWF) and s‐VCAM (soluble vascular cell adhesion molecule) to be markers of endothelial damage during CMV infection (27). In patients with a CMV infection, following a rejection episode we found significantly more endothelial damage as indicated by higher levels of CEC, EC, VWF and s‐VCAM.…”

Section: Discussionmentioning

confidence: 99%

Effects of changing immunosuppressive regimen on the incidence, duration, and viral load of cytomegalovirus infection in renal transplantation: a single center report

Maar

Verschuuren

Heide

et al. 2002

Transplant Infectious Dis

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Background. In this retrospective single center study we have evaluated the relation between the immunosuppressive regimen and the incidence and characteristics of cytomegalovirus (CMV) infection in the setting without CMV prophylaxis from 1989 through 1998. Methods. All (470) first cadaveric renal transplantations in nonsensitized (PRA < 60%) patients were analyzed. Immunosuppression consisted of cyclosporine A (Sandimmune) and prednisolone from 1989 through 2-1993 (S; 189 patients), of cyclosporine microemulsion (Neoral) and prednisolone from 3-1993 through 5-1997 (N; 200 patients) and of mycophenolate mofetil, Neoral and prednisolone from 5-1997 until 1998 (M; 81 patients). The CMV pp65-antigenemia was measured routinely at least once weekly from day 10 till 12 weeks after transplantation or until pp65-antigenemia became negative. No CMV-prophylaxis was given. Results. By changing from Sandimmune to Neoral and by adding mycophenolate mofetil, respectively, we observed a higher frequency of especially secondary CMV infections (S vs. N vs. M, respectively, 28 vs. 50 vs. 63%, P = 0.026; S vs. N, P = 0.027; S vs. M, P = 0.015; and N vs. M, n.s). The CMV infections lasted longer (median duration antigenemia S vs. N vs. M, respectively, 3 vs. 5 vs. 7 weeks, P = 0.0003; S vs. N, P < 0.002; S vs. M, P < 0.001; and N vs. M, P < 0.05). Viral load was higher in M (median maximal pp65-antigenemia S vs. N vs. M, respectively, 19 vs. 14.5 vs. 73, P < 0.01; S vs. N, n.s.; S vs. M, P < 0.001 and N vs. M, P < 0.01). Conclusions. The use of Neoral and the addition of mycophenolate mofetil caused significant changes in the incidence, duration and viral load of CMV infections.

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“…and in RTRs during rejection episodes (12) or severe cytomegalovirus (CMV) infection (13). (14)(15)(16).…”

Section: It Is Now Well Recognized That Disruption Of Endothelial Intmentioning

confidence: 99%

Impact of Immunosuppressive Treatment on Endothelial Biomarkers After Kidney Transplantation

Al-Massarani

Vacher-Coponat

Paul

et al. 2008

American Journal of Transplantation

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Endothelial dysfunction occurs in hemodialysis and kidney-transplanted patients and can be enhanced by immunosuppressive therapy. Circulating endothelial cells (CEC), endothelial microparticles (EMP) and sVCAM-1 provide information on endothelium activation and damage.We compared the impact of two immunosuppressive regimens (CsA/Aza vs. Tac/MMF) on the kinetics of CEC, EMP and sVCAM-1 levels in 52 patients, both before graft and 3, 6, 9 and 12 months after graft, in reference to 50 healthy controls.CEC, EMP and sVCAM-1 levels were significantly decreased 1 year after transplantation (M12) as compared to pretransplant values. At M12, CEC and sVCAM-1 levels were significantly higher than those of controls whereas EMP reached normal values. Nine months postgraft, lower CEC and normalized EMP levels were found in patients receiving cyclosporine microemulsion/ azathioprine (CsA/Aza) when compared to patients treated with tacrolimus/ mycophenolate mofetil (Tac/MMF). Multivariate analysis evidenced positive correlations between CEC and history of cardiovascular diseases and between EMP and cytomegalovirus infection at M12.In conclusion, our combined analysis of endothelial injury markers confirms the favorable impact of renal transplantation on endothelium, and show that CEC levels discriminate treatment-associated endothelial toxicity. These results enlighten the potential of these noninvasive blood biomarkers in indexing vascular injury and optimize therapeutic options.

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Acute rejection before cytomegalovirus infection enhances von Willebrand factor and soluble VCAM-1 in blood

Abstract: CMV infection is associated with vascular damage, and the vascular damage during CMV infection is enhanced if patients experienced acute rejection before CMV infection.

Cited by 28 publications

References 39 publications

Human Cytomegalovirus Infection of Endothelial Cells Triggers Platelet Adhesion and Aggregation

Human Cytomegalovirus Infection of Endothelial Cells Triggers Platelet Adhesion and Aggregation

Effects of changing immunosuppressive regimen on the incidence, duration, and viral load of cytomegalovirus infection in renal transplantation: a single center report

Impact of Immunosuppressive Treatment on Endothelial Biomarkers After Kidney Transplantation

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