title: RCMV increases intimal hyperplasia by inducing inflammation, MCP-1 expression and recruitment of adventitial cells to intima.
abstract: BACKGROUND
  Cytomegalovirus (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.
  
  
  METHODS
  Infrarenal 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.
  
  
  RESULTS
  Intimal 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.
  
  
  CONCLUSIONS
  RCMV 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.
authors.affiliation: Experimental Cardiovascular Research Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Monika K
authors.initials: MK
authors.lastname: Grudzinska
authors.affiliation: Department of General, Vascular and Oncologic Surgery, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Bojakowski
authors.affiliation: Department of General Biochemistry and Nutrition, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Soin
authors.affiliation: Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Stassen
authors.affiliation: Experimental Cardiovascular Research Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Söderberg-Nauclér
authors.affiliation: Experimental Cardiovascular Research Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Piotr
authors.initials: P
authors.lastname: Religa