ROLE OF THE CYTOMEGALOVIRUS SECRETOME IN ACCELERATION OF TVS

巨细胞病毒分泌组在加速 TVS 中的作用

• 批准号: 8173299
• 负责人: JAY A NELSON
• 金额: $ 9.51万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173299
• 关键词: Acceleration; Accounting; Allografting; Atherosclerosis; Blood Vessels; Cells; Computer Retrieval of Information on Scientific Projects Database; Cytomegalovirus; Development; Disease; Funding; Gene Expression Microarray Analysis; Genes; Goals; Grant; Growth Factor; Heart Transplantation; Infection; Institution; Modeling; Organ; Organ Transplantation; Rattus; Research; Research Personnel; Resources; Role; Sclerosis; Solid; Source; Tissues; Transplant Recipients; Transplantation; United States National Institutes of Health; Vascular Diseases; Virus; angiogenesis; cytokine; heart allograft; paracrine; restenosis

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The long-term goal of this project is to determine the role of human cytomegalovirus (HCMV) in the acceleration of vascular diseases such as atherosclerosis, restenosis, and transplant vascular sclerosis (TVS). HCMV is associated with TVS and CR in solid organ transplant patients and we have observed that RCMV significantly accelerates the development of TVS and CR in heart allografts in the rat transplant model. Although we can detect the presence of virus in the transplanted heart throughout the disease course, the number of infected cells in the allograft does not account for the global effects of RCMV infection of the organ in the development of TVS. This lack of correlation suggests that infected cells are influencing the microenvironment via paracrine mechanisms. Analysis of allografts with RCMV-accelerated TVS for host cell gene expression by microarray analysis revealed a significant number of genes involved in tissue remodeling (WH) and angiogenesis (AG) that were highly up-regulated in the organ transplant. We hypothesize that the spectrum of cytokines and growth factors secreted by CMV-infected cells significantly contribute to the acceleration of TVS and CR in heart allografts through the stimulation of WH and AG.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 该项目的长期目标是确定人类巨细胞病毒（HCMV）在诸如动脉粥样硬化，再狭窄和移植血管硬化症（TVS）等血管疾病加速中的作用。 HCMV与固体器官移植患者的TVS和CR相关，我们观察到RCMV在大鼠移植模型中显着加速了TVS和CR的发育。尽管我们可以在整个疾病过程中检测到移植心脏中病毒的存在，但同种异体移植中感染细胞的数量并不能解释器官RCMV感染在电视开发中的全球影响。缺乏相关性表明，受感染的细胞正在通过旁分泌机制影响微环境。通过微阵列分析对使用RCMV加速电视进行宿主细胞基因表达的同种异体移植物的分析表明，在器官移植中高度上调了组织重塑（WH）和血管生成（WH）和血管生成（AG）的大量基因。 我们假设CMV感染细胞分泌的细胞因子和生长因子的光谱通过刺激WH和AG显着促进了心脏同种异体移植物中TV和CR的加速。