Cytomegalovirus infection in heart transplant recipients is associated with impaired endothelial function

Petrakopoulou, Paraskevi; Kübrich, Marion; Pehlivanli, Sinan

doi:10.1016/j.accreview.2004.12.021

Cited by 18 publications

(20 citation statements)

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“…The role of CMV infection in the pathogenesis of cardiac allograft vasculopathy is particularly well documented [Taylor et al, ; Potena and Valantive, ]. Not only does CMV trigger vascular injury, most likely through the induction of inflammation and activation of local antiviral immune response, but also contributes to a general non‐specific immunosuppression [Petrakopoulou et al, ; Rubin, ; Senchenkov et al, ]. Interestingly, the positive outcomes of statins treatment was demonstrated in heart transplant recipient with significantly improved survival, decreased graft rejection and reduced progression of cardiac allograft vasculopathy [Kobashigawa et al, ; Wenke et al, ; Mehra and Raval, ].…”

Section: Discussionmentioning

confidence: 99%

Statins demonstrate a broad anti-cytomegalovirus activity in vitro in ganciclovir-susceptible and resistant strains

et al. 2014

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Vasculoprotective and cholesterol-lowering properties are hallmarks of statins. Recently, statins have been found to exhibit antiviral activity. Little is known about the potential of statins against human cytomegalovirus (HCMV), a risk factor in the pathogenesis of atherosclerosis. In this study, the in vitro anti-CMV activity of four statins (atorva-, fluva-, prava-, and simvastatin) was explored in human aortic endothelial cells (HAEC) and fibroblasts. All statins dose-dependently reduced HCMV titers in both cell types. Whereas atorva-, fluva-, and simvastatin showed comparable EC50 and EC90 within a low micromolar range in HAEC, pravastatin exhibited only limited effects. In metabolite rescue experiments, mevalonate almost completely abrogated the anti-CMV activity of all statins, whereas cholesterol failed to counteract the effects. Geranylgeranyl-pyrophosphate partially reversed the anti-CMV activity of most statins, suggesting an involvement of the non-sterol isoprenoid arm of the mevalonate pathway as the mode-of-action. The accumulation of immediate early viral antigens was blocked after 1 dpi onwards, and early and late antigen expression was completely abolished in HAEC. The antiviral activity of statins was comparable to ganciclovir and was retained in a ganciclovir-resistant HCMV strain. These findings provide new insight into the beneficial effects of statins, adding antiviral activity against HCMV to their list of pleïotropic properties, and support further clinical investigations on combined therapy for the management of active HCMV disease.

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Section: Discussionmentioning

confidence: 99%

Statins demonstrate a broad anti-cytomegalovirus activity in vitro in ganciclovir-susceptible and resistant strains

et al. 2014

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“…In vitro , CMV infection has been shown to activate the P38‐mitogen‐activated protein kinase (MAPK) signalling pathway and up‐regulate phosphatase and tensin homologue [30,31]. Via this pathway, endothelial nitric oxide synthase is inhibited and reduced nitric oxide (NO) production leads to endothelial dysfunction [32,33]. The association between CMV and endothelial dysfunction has been hypothesized further to be one possible pathological mechanism of hypertension [33].…”

Section: Discussionmentioning

confidence: 99%

Relation of high cytomegalovirus antibody titres to blood pressure and brachial artery flow-mediated dilation in young men: the Cardiovascular Risk in Young Finns Study

Haarala¹,

Kähönen

Lehtimäki

et al. 2012

Clinical and Experimental Immunology

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SummaryHuman cytomegalovirus (CMV) infection is associated with a higher risk of cardiovascular disease in immunocompromised organ transplant patients. It has been linked with the pathogenesis of elevated arterial blood pressure. However, controversy exists as to whether CMV infection is associated with endothelial function, and little is known about its role as a potential risk factor for early atherosclerosis development at a young age. We aimed to discover if CMV antibody titres are associated with early vascular changes (carotid intima-media thickness, carotid artery distensibility and brachial artery flowmediated dilation), blood pressure elevation or other traditional cardiovascular risk factors. CMV antibody titres were measured in 1074 women and 857 men (aged 24-39 years) taking part in the Cardiovascular Risk in Young Finns study. CMV antibody titres were significantly higher in women compared to men. In men, high CMV antibody titres were associated directly with age (P < 0·001) and systolic (P = 0·053) and diastolic (P = 0·002) blood pressure elevation, and associated inversely with flow-mediated dilation (P = 0·014). In women, CMV antibody titres did not associate with any of the analysed parameters. In a multivariate regression model, which included traditional atherosclerotic risk factors, CMV antibody titres were independent determinants for systolic (P = 0·029) and diastolic (P = 0·004) blood pressure elevation and flow-mediated dilation (P = 0·014) in men. High CMV antibody titres are associated independently with blood pressure and brachial artery flow-mediated dilation in young men. This association supports the hypothesis that common CMV infection and/or an immune response to CMV may lead to impaired vascular function at a young age.

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“…Influence of CMV on the vascular damage is potentially strengthened by its ability to increase the cellular expression of adhesion molecules and to increase the secretion of growth factors such as TGF‐β1 and PDGF (11, 18). In addition, CMV infection is also likely to impair the nitric oxide pathway and to induce endothelial dysfunction (19).…”

Section: Discussionmentioning

confidence: 99%

Risk Factors and Long-Term Outcome of Transplant Renal Artery Stenosis in Adult Recipients After Treatment by Percutaneous Transluminal Angioplasty

Audard

Matignon

Hémery³

et al. 2006

American Journal of Transplantation

147

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Transplant renal artery stenosis (TRAS) is a common complication of kidney transplantation but attempts to identify predisposing risk factors for TRAS have yielded conflicting results. In order to determine the predisposing factors for transplant (TRAS), we retrospectively reviewed the records of 29 renal allograft recipients with TRAS treated with percutaneous transluminal angioplasty (PTA). The TRAS group was compared with a case-control group of 58 patients. Predisposing factors for TRAS included CMV infection (41.4% vs. 12.1% p = 0.0018) and initial delayed graft function (DGF) (48.3% vs. 15.5% p = 0.0018), respectively in the TRAS and the control group. Acute rejection occurred more frequently in patients from the TRAS group (48.3%) compared with the control group (27.6%), although the difference was not significant (p = 0.06). In a multivariate analysis, only CMV infection (p = 0.005) and DGF (p = 0.009) appear to be significantly and independently associated with TRAS. The long-term graft survival was significantly higher in the control group, compared with the TRAS group (p = 0.03). Our study suggests that CMV infection and DGF are two reliable risk factors for TRAS. Despite treatment by PTA with primary successful results, TRAS significantly affects long-term graft outcome. † These authors contributed equally to this study.

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Cytomegalovirus infection in heart transplant recipients is associated with impaired endothelial function

Cited by 18 publications

References 0 publications

Statins demonstrate a broad anti-cytomegalovirus activity in vitro in ganciclovir-susceptible and resistant strains

Statins demonstrate a broad anti-cytomegalovirus activity in vitro in ganciclovir-susceptible and resistant strains

Relation of high cytomegalovirus antibody titres to blood pressure and brachial artery flow-mediated dilation in young men: the Cardiovascular Risk in Young Finns Study

Risk Factors and Long-Term Outcome of Transplant Renal Artery Stenosis in Adult Recipients After Treatment by Percutaneous Transluminal Angioplasty

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