Association between Prior Cytomegalovirus Infection and the Risk of Restenosis after Coronary Atherectomy

Zhou, Yi; Leon, Martin B.; Waclawiw, Myron A.; Popma, Jeffery J.; Yu, Zu Xi; Finkel, Toren; Epstein, Stephen E.

doi:10.1056/nejm199608293350903

Cited by 428 publications

(284 citation statements)

References 26 publications

Supporting

Mentioning

256

Contrasting

Unclassified

Order By: Relevance

“…HCMV infection has been associated with several forms of vascular pathology including transplantation-associated atherosclerosis (Grattan et al, 1989;Normann et al, 1991;Koskinen et al, 1993;Skowronski et al, 1993;Lautenschlager et al, 1997a), restenosis after balloon angioplasty (Speir et al, 1994;Zhou et al, 1996) and even the development of native atherosclerotic lesions (Hendrix et al, 1990;Melnick et al, 1994;Horvath et al, 2000;Streblow et al, 2001;Levi, 2001). However, the pathogenic mechanisms by which HCMV infection contributes to these processes remain to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Synergistic induction of intercellular adhesion molecule-1 by the human cytomegalovirus transactivators IE2p86 and pp71 is mediated via an Sp1-binding site

Kronschnabl¹,

Stamminger²

2003

Journal of General Virology

View full text Add to dashboard Cite

Human cytomegalovirus (HCMV) infection of transplant recipients is frequently associated with allograft vasculopathy and rejection. One potential mechanism is vascular injury from HCMVtriggered, immunologically mediated processes. HCMV infection has been shown to increase the expression of intercellular adhesion molecule-1 (ICAM-1). The objective of this study was to determine the molecular basis of HCMV-enhanced ICAM-1 gene expression. Transient transfection experiments identified the IE2p86 protein as a potent activator of the ICAM-1 promoter. The tegument protein pp71 showed a strong synergistic effect on IE2p86-mediated ICAM-1 promoter activation. Mutagenesis experiments defined a DNA element from 2110 to 242 relative to the transcription start site as responsive for IE2p86. Further point mutations within this DNA element identified an Sp1-binding site that was essential for strong synergistic activation by IE2p86 and pp71. To confirm the activation of ICAM-1 gene expression, human fibroblasts (HFF) as well as endothelial cells (HUVEC) were infected with recombinant IE2p86-and pp71-expressing baculoviruses, respectively. In FACS analysis, a synergistic induction of ICAM-1 was detectable when cells were co-infected with the two recombinant baculoviruses. These findings clearly demonstrate that IE2p86 and pp71 are crucial regulatory factors for HCMV-induced ICAM-1 upregulation. INTRODUCTIONHuman cytomegalovirus (HCMV), a b-herpesvirus, is a ubiquitous human pathogen with a prevalence of infection in the adult population of 50-90 %. Although HCMV rarely causes severe disease on primary infection in immunocompetent people, it represents a highly pathogenic agent for immunosuppressed patients such as transplant recipients, as well as newborns, and establishes lifelong persistence in the infected host (Alford & Britt, 1990). So far, the exact site of latency is still uncertain; monocytes, haematopoietic precursor cells and endothelial cells have been discussed as potential reservoirs for latent HCMV (Fish et al., 1995;Sindre et al., 1996).Recent evidence suggests that HCMV not only causes acute infection in transplanted patients but may also be associated with extensive transplant vasculopathy, ultimately leading to chronic allograft rejection (Grattan et al., 1989;Skowronski et al., 1993;Koskinen et al., 1993;Lautenschlager et al., 1997a;Schnitzler et al., 1997;Borchers et al., 1999). One of the molecular mechanisms underlying the acceleration of vascular disease processes by HCMV infection may be enhancement of transplant immunogenicity. Several studies indicate that this involves the HCMV-induced upregulation of cellular adhesion molecules, which augments the adherance and infiltration of inflammatory cells that are capable of promoting vascular disease (Einsele et al., 1994;Lemstrom et al., 1995;Steinhoff et al., 1995;Koskinen et al., 1996;Yilmaz et al., 1996; Martelius et al., 1998;Waldman et al., 1998;Lautenschlager et al., 1999;The et al., 2001). For instance, cell culture experiments have demonstrated that...

show abstract

Section: Discussionmentioning

confidence: 99%

Synergistic induction of intercellular adhesion molecule-1 by the human cytomegalovirus transactivators IE2p86 and pp71 is mediated via an Sp1-binding site

Kronschnabl¹,

Stamminger²

2003

Journal of General Virology

View full text Add to dashboard Cite

show abstract

“…In cardiac recipients studied with vascular ultrasound, prolonging prophylaxis (3 vs. 1 mo) slowed vascular disease over the first year after transplantation (115). CMV seropositivity was also linked to restenosis after coronary angioplasty and atherectomy (116). Similarly, in renal transplantation, CMV infection was an independent risk factor in a multivariate analysis of arterial stenosis (117)(118)(119).…”

Section: Nonimmune Pathways In Cmv-associated Allograft Injurymentioning

confidence: 98%

The Cell Biology of Cytomegalovirus: Implications for Transplantation

Kaminski

Fishman

2016

American Journal of Transplantation

View full text Add to dashboard Cite

Interpretation of clinical data regarding the impact of cytomegalovirus (CMV) infection on allograft function is complicated by the diversity of viral strains and substantial variability of cellular receptors and viral gene expression in different tissues. Variation also exists in nonspecific (monocytes and dendritic cells) and specific (NK cells, antibodies) responses that augment T cell antiviral activities. Innate immune signaling pathways and expanded pools of memory NK cells and cd T cells also serve to amplify host responses to infection. The clinical impact of specific memory T cell anti-CMV responses that cross-react with graft antigens and alloantigens is uncertain but appears to contribute to graft injury and to the abrogation of allograft tolerance. These responses are modified by diverse immunosuppressive regimens and by underlying host immune deficits. The impact of CMV infection on the transplant recipient reflects cellular changes and corresponding host responses, the convergence of which has been termed the "indirect effects" of CMV infection. Future studies will clarify interactions between CMV infection and allograft injury and will guide interventions that may enhance clinical outcomes in transplantation.

show abstract

“…4 These effects may enhance the proliferation of smooth muscle cells or inhibit apoptosis, either of which may contribute to accelerated atherosclerosis. Prior infection with CMV has been suggested as a strong independent risk factor for restenosis after coronary atherectomy, 15 and there is a graded relation between the odds of intimal-medial thickening and levels of CMV antibodies that remained significant after adjustment for the main cardiovascular risk factors. 16,17 Other viruses have been "accused" as well, for example, the hepatitis A (HAV) virus.…”

Section: The Infectious Theorymentioning

confidence: 99%

Viral load of the human immunodeficiency virus could be an independent risk factor for endothelial dysfunction

et al. 2005

View full text Add to dashboard Cite

SummaryBackground: Recent reports of myocardial infarction in young persons infected with human immunodeficiency virus (HIV) who are receiving protease inhibitor therapy have raised concerns about premature coronary artery disease in this population. However, endothelial dysfunction, hypercoagulability, hypertriglyceridemia, and abnormal coronary artery pathology have been observed in association with HIV infection prior to the availability of protease inhibitor therapy.Hypothesis: The study was undertaken to determine the association between endothelial function, viral load, CD4+ count, and other well-established risk factors for atherosclerosis.Methods: This prospective, case-controlled study compared viral (HIV) load and the CD4+ T-lymphocyte count and endothelial function in 24 HIV-positive carriers. Brachial artery diameter, HIV viral load, and CD4 count were measured.Results: We found that viral load correlated inversely with endothelial function; the higher the viral load, the worse the endothelial dysfunction (p < 0.005).Conclusion: High viral load appears to be associated with endothelial dysfunction in patients with HIV. This preliminary observation supports the infectious theory that viruses may play an important role in the pathogenesis of atherosclerosis.

show abstract

Association between Prior Cytomegalovirus Infection and the Risk of Restenosis after Coronary Atherectomy

Abstract: Prior infection with CMV is strong independent risk factor for restenosis after coronary atherectomy. If confirmed, these findings may help identify patients at risk for restenosis.

Cited by 428 publications

References 26 publications

Synergistic induction of intercellular adhesion molecule-1 by the human cytomegalovirus transactivators IE2p86 and pp71 is mediated via an Sp1-binding site

Synergistic induction of intercellular adhesion molecule-1 by the human cytomegalovirus transactivators IE2p86 and pp71 is mediated via an Sp1-binding site

The Cell Biology of Cytomegalovirus: Implications for Transplantation

Viral load of the human immunodeficiency virus could be an independent risk factor for endothelial dysfunction

Contact Info

Product

Resources

About