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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 该项目的长期目标是确定人类巨细胞病毒（HCMV）在加速动脉粥样硬化、再狭窄和移植血管硬化（TVS）等血管疾病中的作用。 HCMV 与实体器官移植患者的 TVS 和 CR 相关，我们观察到 RCMV 显着加速大鼠移植模型中同种异体心脏移植物中 TVS 和 CR 的发展。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，但同种异体移植物中受感染细胞的数量并不能解释器官的 RCMV 感染对 TVS 发展的整体影响。这种相关性的缺乏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 TVS 的同种异体移植物进行宿主细胞基因表达分析，发现大量参与组织重塑 (WH) 和血管生成 (AG) 的基因在器官移植中高度上调。 我们假设 CMV 感染细胞分泌的细胞因子和生长因子谱通过刺激 WH 和 AG 显着促进同种异体心脏移植物中 TVS 和 CR 的加速。