COLLAGEN GENE EXPRESSION AND ATHEROSCLEROSIS

胶原蛋白基因表达与动脉粥样硬化

• 批准号: 7413535
• 负责人: BARBARA A SMITH
• 金额: $ 29.83万
• 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/7413535
• 关键词: antihypercholesterolemic agent; atherosclerosis; atherosclerotic plaque; cell proliferation; clinical research; collagen; gene induction /repression; genetic transcription; genetically modified animals; histocompatibility gene; interferon gamma; laboratory mouse; methylation; protein metabolism; transcription factor; 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）：该计划项目的主题是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。 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）将扩展她关于 myb 家族和 NFkB 在胶原蛋白和弹性蛋白基因表达以及 VSMC 增殖的协调调节中的作用的发现。 将研究 B-Myb 抑制基质基因转录的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）将研究 A2bAR 基因表达的调节以及 B-Myb 在增殖诱导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，重点关注 VSMC 增殖、基质生成和血管张力。 Herbert Kagan 博士（项目 3）将关注他的实验室最近发现的赖氨酰氧化酶 (LO)（细胞外结缔组织交联酶）与表面膜整合素和 VSMC 细胞核之间的相互作用。 将研究 LO 诱导 VSMC 趋化性、抑制细胞增殖和刺激胶原蛋白产生所涉及的受体和机制。 Barbara Smith 博士（项目 4）是该项目的新项目负责人，她将扩展她的转录。 她最近发现了一种转录共调节因子（CIITA），它在炎症过程中被诱导，并起到减少胶原蛋白转录的作用。 她还将研究他汀类药物在胶原蛋白基因转录中的作用。 她还将研究他汀类药物在胶原蛋白基因转录中的作用。 总体而言，该计划项目的研究将在体外使用 VSMC 和血管损伤的转基因小鼠模型进行。 该计划由管理核心和生物模型核心支持。 由 Barbara Schreiber 博士领导的 BioModel Core 提供各种服务来支持这些项目。 特别值得注意的是，Schreiber 博士引入了一种小鼠股动脉损伤模型，该模型会产生再狭窄和动脉粥样硬化样病变。 每个项目都将利用该模型来测试体内假设。