MECHANISMS OF AORTIC FIBROSIS

主动脉纤维化的机制

• 批准号: 7413527
• 负责人: Herbert Marcus Kagan
• 金额: $ 30.73万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7413527
• 关键词: amine oxidoreductase; atherosclerosis; biological signal transduction; cell surface receptors; chemotaxis; clinical research; collagen; enzyme mechanism; gene expression; histones; immunocytochemistry; in situ hybridization; laboratory mouse; laboratory rat; lysine; protein localization; receptor binding; tissue /cell culture; vascular smooth muscle

DESCRIPTION (provided by applicant): This Program Project retains as its theme the investigation of interacting mechanisms that regulate vascular smooth muscle cell (VSMC) proliferation and extracellular matrix production. These features are central to the development of atherosclerotic lesions. Dr. Gail Sonenshein (Project 1) will extend her findings on the roles of the myb family and NFkB in the coordinated regulation of collagen and elastin gene expression and VSMC proliferation. The mechanism of repression of matrix gene transcription by B-Myb and the roles of phosphorylation and protein interactions will be investigated. Dr. Katya Ravid (Project 2) will investigate the regulation of expression of the A2bAR gene and the role of B-Myb in proliferation-induced upregulation of this gene. She will also identify the role of this receptor in vascular function, focusing on VSMC proliferation, matrix production and vascular tone. Dr. Herbert Kagan (Project 3), will be concerned with the interactions recently found in his laboratory between lysyl oxidase (LO), the extrecellular connective tissue crosslinking enzyme, and surface membrane integrins and nuclei of VSMC. The receptors and mechanisms involved in the induction by LO of VSMC chemotaxis, suppression of cell proliferation and stimulation of collagen production will be investigated. Dr. Barbara Smith (Project 4), a new Project Leader in this Program Project, will extend her transcription. She has recently identified a transcription co-regulator (CIITA) that is induced during inflammation and acts to decrease collagen transcription. She will also investigate the role of statins in collagen gene transcription. She will also investigate the role of statins in collagen gene transcription. Overall, the research of this Program Project will be conducted with VSMCs in vitro and with transgenic mouse models of vascular injury. The program is supported by an Administrative Core and a BioModel Core. The BioModel Core, directed by Dr. Barbara Schreiber, provides a variety of services to support these projects. Of particular note, Dr. Schreiber has introduced a mouse femoral artery injury model with generates restenotic and atherosclerotic-like lesions. Each project will avail itself of this model to test hypotheses in vivo.

描述（由申请人提供）：该程序项目保留为主题，研究调节血管平滑肌细胞（VSMC）增殖和细胞外基质产生的相互作用机制的研究。 这些特征对于动脉粥样硬化病变的发展至关重要。 Gail Sonenshein博士（项目1）将扩展她对MYB家族和NFKB在胶原蛋白和弹性蛋白基因表达和VSMC增殖的协调调节中的作用的发现。 将研究B-MYB对基质基因转录的抑制机制以及磷酸化和蛋白质相互作用的作用。 Katya Ravid博士（项目2）将调查A2BAR基因表达的调节以及B-Myb在增殖引起的该基因上调中的作用。 她还将确定该受体在血管功能中的作用，重点是VSMC增殖，基质产生和血管张力。 赫伯特·卡根（Herbert Kagan）博士（项目3）将与他的实验室中最近在赖氨酸氧化酶（LO），细胞外结缔组织交联酶以及VSMC的表面膜整合蛋白和核之间发现的相互作用有关。 将研究通过VSMC趋化性LO诱导的受体和机制，抑制细胞增殖和胶原蛋白产生的刺激。 该计划项目的新项目负责人芭芭拉·史密斯（Barbara Smith）博士将扩展其转录。 她最近确定了在炎症期间诱导的转录共同调节剂（CIITA），并作用于减少胶原蛋白转录。 她还将研究他汀类药物在胶原基因转录中的作用。 她还将研究他汀类药物在胶原基因转录中的作用。 总体而言，该计划项目的研究将在体外和VSMC进行血管损伤的转基因小鼠模型进行。 该程序由行政核心和生物模型核心支持。 由Barbara Schreiber博士执导的生物模型核心提供了多种支持这些项目的服务。 特别值得注意的是，Schreiber博士已经引入了一种小鼠股动脉损伤模型，该模型具有再狭窄和类似动脉粥样硬化的病变。 每个项目都将利用该模型在体内测试假设。