RCMV increases intimal hyperplasia by inducing inflammation, MCP-1 expression and recruitment of adventitial cells to intima

Monika K Grudzinska,Frank Stassen,Piotr Religa,Krzysztof Bojakowski,Cecilia Söderberg-Nauclér,Joanna Soin

doi:10.1186/2042-4280-1-7

Monika K Grudzinska, Frank Stassen + Show 4 more

Open Access

https://doi.org/10.1186/2042-4280-1-7

Copy DOI

Abstract

BackgroundCytomegalovirus (CMV) infection has been associated with accelerated transplant vasculopathy. In this study, we assessed the effects of acute rat CMV (RCMV) infection on vessel remodeling in transplant vasculopathy, focusing on allograft morphology, inflammation and contribution of adventitial cells to intimal hyperplasia.MethodsInfrarenal aorta was locally infected with RCMV and transplanted from female F344 rats to male Lewis rats. Graft samples were collected 2 and 8 weeks after transplantation and analyzed for intimal hyperplasia, collagen degradation and inflammation. Transplantation of aorta followed by transplantation of RCMV infected and labeled isogenic adventitia were performed to study migration of adventitial cells towards the intima.ResultsIntimal hyperplasia was increased threefold in infected allografts. RCMV induced apoptosis in the media, expression of matrix metalloproteinase 2, and decreased collagen deposits. Macrophage infiltration was increased in the infected allografts and resulted in increased production of MCP-1. RCMV-infected macrophages were observed in the adventitia and intima. Cells derived from infected adventitia migrated towards the intima of the allograft.ConclusionsRCMV enhances infiltration of macrophages to the allografts, and thereby increases MCP-1 production and inflammation, followed by recruitment of adventitial cells to the intima and accelerated intimal hyperplasia.

Highlights

Cytomegalovirus (CMV) infection has been associated with accelerated transplant vasculopathy
rat CMV (RCMV) infection of aortic allografts enhances intimal hyperplasia and media destruction, and decreases extracellular matrix deposition in the allograft To examine how RCMV infection affects arterial remodeling and intimal hyperplasia, we measured the crosssectional area and circumference of the intima and media in the tissue sections and counted the number of cell nuclei counterstained with hematoxylin and cells of SMa-actin phenotype in both media and intima (Figure 1A)
The number of cells was increased in the intima of RCMV-infected allografts at 8 weeks after transplantation compared to uninfected allografts at the same time point

Summary

Introduction

Cytomegalovirus (CMV) infection has been associated with accelerated transplant vasculopathy. We assessed the effects of acute rat CMV (RCMV) infection on vessel remodeling in transplant vasculopathy, focusing on allograft morphology, inflammation and contribution of adventitial cells to intimal hyperplasia. Cytomegalovirus (CMV) is a well-known risk factor for late allograft dysfunction and is associated with atherosclerosis and restenosis after angioplasty [1,2,3,4,5,6]. In the early phase of TV, injured vessels contain predominantly macrophages and a few subendothelial lymphocytes (T, B, and natural killer cells); late vascular lesions are associated with a thickened intima containing cells of Clinical data and animal studies suggest that CMV contributes to the development of TV [12]. Deletion of the US28 rat homolgue R33 reduces the capacity of CMV to accelerate chronic rejection and TV in a rat model [22]

Methods

Results

Discussion

Conclusion