Administrative

描述(由申请者提供)：本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。这些特征是动脉粥样硬化病变发展的中心。Gail Sonenshein博士(项目1)将扩展她关于MYB家族和NFkB在协调调节胶原和弹性蛋白基因表达以及VSMC增殖中的作用的研究结果。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将被研究。Katya Ravid博士(项目2)将研究A2bAR基因的表达调控以及B-Myb在增殖诱导该基因上调中的作用。她还将确定这种受体在血管功能中的作用，重点是VSMC增殖、基质产生和血管紧张性。Herbert Kagan博士(项目3)将关注最近在他的实验室中发现的细胞外结缔组织交联酶赖氨酰氧化酶(LO)与VSMC表面膜整合素和细胞核之间的相互作用。LO诱导VSMC趋化、抑制细胞增殖和刺激胶原生成的受体和机制将被研究。芭芭拉·史密斯博士(项目4)，本计划项目的新项目负责人，将延长她的转录。她最近发现了一种转录辅助调节因子(CIITA)，它在炎症过程中被诱导，并起到减少胶原转录的作用。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，该项目的研究将在体外利用血管平滑肌细胞和血管损伤的转基因小鼠模型进行。该计划由一个管理核心和一个生物模型核心支持。由Barbara Schreiber博士指导的BioModel Core提供各种服务来支持这些项目。特别值得注意的是，Schreiber博士介绍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。每个项目都将利用这一模型在体内测试假设。

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.