鼠巨细胞病毒感染导致鼠主动脉同种异体移植模型中移植动脉硬化的水平增加。

Murine cytomegalovirus infection leads to increased levels of transplant arteriosclerosis in a murine aortic allograft model.

机构信息

Department of Cardiac Surgery, Friedrich-Alexander University Erlangen-Nuremberg, Germany.

出版信息

Transplantation. 2010 Aug 27;90(4):373-9. doi: 10.1097/TP.0b013e3181e8a699.

DOI:10.1097/TP.0b013e3181e8a699

PMID:20585280

Abstract

INTRODUCTION

Cytomegalovirus infection after heart transplantation is considered as risk factor for the development of transplant arteriosclerosis. Therefore, the aim of this study was to investigate the effect of murine cytomegalovirus (MCMV) as a single risk factor on transplant arteriosclerosis in an experimental aortic allograft model.

METHODS

Major histocompatibility complex class I-mismatched aortas of C.B10-H2(b)/LilMcdJ donor were transplanted into BALB/c recipients, which were either mock-infected or infected with MCMV (strain Smith) on day 7 and harvested 37 days after transplantation. In one experimental group animals received a daily dose of everolimus to increase the viral load of recipients. Grafts were analyzed by histology, morphometry, and immunofluorescence. Intragraft cytokine mRNA production was analyzed by real-time polymerase chain reaction (PCR), and persistence of cytomegalovirus infection was confirmed by TaqMan PCR.

RESULTS

After infection with MCMV, there was significantly more intimal proliferation when compared with uninfected controls (intimal proliferation 83.5%+/-9.6% [MCMV] vs. 43.9%+/-5.1% [MCMV]), indicating that MCMV plays a role in the development of transplant arteriosclerosis. Even after treatment with everolimus, MCMV infection pronounced significantly more intimal proliferation (intimal proliferation 52.5%+/-7.3% [MCMV] vs. 20.2%+/-1.7% [MCMV]). Intragraft mRNA expression showed significantly higher production of CD62E, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 after infection with MCMV. Cellular infiltration revealed significantly more CD4, CD8, and dendritic cells. We could also confirm the presence of MCMV for the duration of the experimental protocol by PCR within the spleen, liver, salivary glands, lung, and the aortic transplant.

CONCLUSION

These data suggest that MCMV infection plays an important role in the development of transplant arteriosclerosis.

摘要

简介

心脏移植后巨细胞病毒感染被认为是移植动脉硬化发展的危险因素。因此，本研究的目的是在实验性主动脉同种异体移植模型中，研究鼠巨细胞病毒（MCMV）作为单一危险因素对移植动脉硬化的影响。

方法

主要组织相容性复合物 I 类错配的 C.B10-H2(b)/LilMcdJ 供体主动脉移植到 BALB/c 受体中，受体在第 7 天被模拟感染或 MCMV（Smith 株）感染，并在移植后 37 天收获。在一个实验组中，动物接受依维莫司的每日剂量以增加受者的病毒载量。通过组织学、形态计量学和免疫荧光分析移植。通过实时聚合酶链反应（PCR）分析移植内细胞因子 mRNA 产生，通过 TaqMan PCR 确认巨细胞病毒感染的持续存在。

结果

MCMV 感染后，与未感染对照组相比，内膜增殖明显增加（内膜增殖 83.5%+/-9.6%[MCMV] vs. 43.9%+/-5.1%[MCMV]），表明 MCMV 在移植动脉硬化的发展中起作用。即使在依维莫司治疗后，MCMV 感染也显著增加了内膜增殖（内膜增殖 52.5%+/-7.3%[MCMV] vs. 20.2%+/-1.7%[MCMV]）。MCMV 感染后，移植内 mRNA 表达显示 CD62E、细胞间黏附分子-1 和血管细胞黏附分子-1 的产生显著增加。细胞浸润显示 CD4、CD8 和树突状细胞显著增加。我们还可以通过 PCR 在脾脏、肝脏、唾液腺、肺和主动脉移植中证实 MCMV 在整个实验过程中的存在。