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Published on: July 9, 2020
RCMV increases intimal hyperplasia by inducing inflammation, MCP-1 expression and recruitment of adventitial cells to
Monika K Grudzinska1, Krzysztof Bojakowski2, Joanna Soin3
1Experimental Cardiovascular Research Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
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.
Insights
Rat cytomegalovirus (CMV) infection accelerates transplant vasculopathy by increasing macrophage infiltration and inflammation. This leads to adventitial cell recruitment and heightened intimal hyperplasia in allografts.
Area of Science:
- Vascular Biology
- Transplantation Immunology
- Virology
Background:
- Cytomegalovirus (CMV) infection is linked to accelerated transplant vasculopathy.
- This study investigates the impact of acute rat CMV (RCMV) infection on vessel remodeling in transplant vasculopathy.
Purpose of the Study:
- To assess the effects of RCMV infection on allograft morphology, inflammation, and adventitial cell contribution to intimal hyperplasia.
Main Methods:
- Rats underwent infrarenal aorta transplantation with local RCMV infection.
- Graft analysis included intimal hyperplasia, collagen degradation, and inflammation at 2 and 8 weeks.
- Adventitial cell migration to the intima was studied using labeled isogenic adventitia.
Main Results:
- RCMV infection increased intimal hyperplasia threefold in allografts.
- RCMV induced medial apoptosis, matrix metalloproteinase 2 expression, and reduced collagen.
- Macrophage infiltration and MCP-1 production increased, with RCMV-infected macrophages found in adventitia and intima.
Conclusions:
- RCMV infection enhances macrophage infiltration and MCP-1 production, promoting inflammation.
- This process recruits adventitial cells to the intima, accelerating intimal hyperplasia.
- RCMV significantly contributes to the pathogenesis of transplant vasculopathy.
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