ENDOTHELIAL CELL SIGNALING AND CARDIAC ANGIOGENESIS

内皮细胞信号传导和心脏血管生成

• 批准号: 6638573
• 负责人: ROBERT D ROSENBERG
• 金额: $ 182.78万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6638573
• 关键词: angiogenesis; heart circulation; vascular endothelium

The Specialized Center of Research (SCOR) in Ischemic Heart Disease will bring together faculty with clinical and basic science appointments at the Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School (HMS) as well as Division of Health, Science and Technology (HST) and Department of Biology at the Massachusetts Institute of Technology. The Principal goal of this research is to lay down a foundation for new therapeutic approaches to the ischemic heart disease that will be at the core of our ability to design novel ways of stimulating collateral vessel growth in the diseased heart. Thus, the program combines basic, applied, and clinical research in vascular biology and molecular medicine. In addition, considerable emphasis is placed on the development of novel clinical and functional endpoints needed to assess the efficacy of angiogenic therapy. Recent investigations have conclusively demonstrated vascular bed- and milieu-specific regulation of endothelial cell function. Thus, there is every reason to expect that signaling events involved- both to and from endothelial cells are also vascular-bed and organ specific. Therefore, any investigation of endothelial cell signaling should be linked to the local context. With this concept in mind, three projects in this SCOR application are designed to assess endothelial cell signaling at several different levels. These include: 1) Identification and characterization of myocyte-derived stimulators of angiogenesis; 2) Molecular analysis of a novel syndecan-4-dependent signaling pathway in endothelial cells that is involved in mediation of bFGF-dependent angiogenesis; 3) The study of vascular bed-specific endothelial cell transcription. In combination, these projects provide a comprehensive approach to the role of endothelial cell diversity and inside-out as well outside-in signaling in regulation of local processes. The clinical project in this SCOR application addresses two fundamental issues in therapeutic application of this research- Development of effective local delivery strategies and characterization of novel clinical end-points that would be useful in large scale trials of angiogenic therapy. These projects are supported by Core laboratories that provide critical expertise in large and small bore magnetic resonance imaging and generation and evaluation of transgenic mice. Although our focus is primarily on cardiovascular applications, this program will provide broad biological insights into endothelial cell biology, angiogenesis and signal transduction that will be relevant to lung, blood and other diseases.

缺血性心脏病专业研究中心 (SCOR) 将汇集贝斯以色列女执事医疗中心 (BIDMC) 和哈佛医学院 (HMS) 以及麻省理工学院健康、科学与技术部 (HST) 和生物系的临床和基础科学教职人员。这项研究的主要目标是为缺血性心脏病的新治疗方法奠定基础，这将是我们设计刺激患病心脏侧支血管生长的新方法的能力的核心。因此，该项目结合了血管生物学和分子医学的基础、应用和临床研究。此外，还非常重视开发评估血管生成疗法疗效所需的新型临床和功能终点。最近的研究最终证明了内皮细胞功能的血管床和环境特异性调节。因此，有充分的理由预期所涉及的内皮细胞信号转导事件也是血管床和器官特异性的。因此，对内皮细胞信号传导的任何研究都应与当地环境联系起来。考虑到这一概念，该 SCOR 应用中的三个项目旨在评估多个不同级别的内皮细胞信号传导。这些包括：1）肌细胞来源的血管生成刺激物的鉴定和表征； 2) 内皮细胞中新型 Syndecan-4 依赖性信号通路的分子分析，该通路参与介导 bFGF 依赖性血管生成； 3）血管床特异性内皮细胞转录的研究。结合起来，这些项目提供了一种全面的方法来研究内皮细胞多样性和由内而外以及由外而内信号传导在局部过程调节中的作用。该 SCOR 应用中的临床项目解决了该研究的治疗应用中的两个基本问题 - 开发有效的局部递送策略和表征新的临床终点，这将有助于血管生成治疗的大规模试验。这些项目得到了核心实验室的支持，这些实验室在大孔和小孔磁共振成像以及转基因小鼠的生成和评估方面提供关键的专业知识。尽管我们的重点主要是心血管应用，但该项目将为与肺、血液和其他疾病相关的内皮细胞生物学、血管生成和信号转导提供广泛的生物学见解。