SPECIALIZED CENTER OF RESEARCH IN ARTERIOSCLEROSIS

这是一个申请，以形成一个新的SCOR计划致力于病理学 人类动脉粥样硬化。该提案由六个项目组成，这些项目摘自 病理学，血液学，检验医学，生物化学系， 和遗传学。每种方法都围绕着测试特定的现有 一种试图解释动脉粥样硬化病变起源的假说 或这些病变的进展到临床上有意义的生活- 有血管阻塞的危险。这些项目是由一个 致力于人类病变病理学的核心实验室。 SCOR的第一个焦点是对当前主要的 斑块中平滑肌细胞的起源。斑块有可能 从病毒致突变事件开始，通过系统地研究 空斑病毒与血管壁细胞病毒学研究。这个 斑块起源于发育的可能性由一个 克隆动脉粥样硬化特有表达基因的尝试 斑块。用X-射线衍射仪在新的水平上研究病变的单克隆性。 链接的RNA多态，以确定何时以及如何出现单克隆性。 斑块起源于炎症过程的可能性是 通过观察斑块巨噬细胞在表达生长中的作用来检验 各种因素。所有这些研究都是在人体组织中进行的。测试 假设将取决于我们证明预期结果的能力。 结果在人体内造成损害。 第二个重点领域，斑块进展的研究，也强调 人体病变中炎症机制的研究。两个项目包括 斑块巨噬细胞分泌细胞因子调控的研究进展 控制白细胞黏附分子的表达。除了……之外 炎症过程的研究，一个项目是针对脂蛋白的 脂肪酶。斑块巨噬细胞和平滑肌细胞都是 被研究为脂蛋白脂肪酶的来源，脂蛋白脂肪酶是形成游离的必需酶 脂肪酸。该项目研究了这种酶的表达控制。 通过谱系特异性顺式作用元件和激素反应元件 各种因素。 最后，SCOR提出了治疗斑块的新的和独特的方法 通过提议使用重组形式的膜联蛋白来促进凝血剂事件 磷酸-丝氨酸结合蛋白作为一种可定位的抗凝剂 在血栓形成的地方。

This is an application to form a new SCOR program devoted to the pathology of human atherosclerosis. The proposal consists of six projects drawn from the Department of Pathology, Hematology, Laboratory Medicine, Biochemistry, and Genetics. Each is centered around testing a specific existing hypothesis that attempts to explain the origins of atherosclerotic lesions or the progression of these lesions to a clinically significant, life- threatening vascular obstruction. The projects are drawn together by a core laboratory devoted to the pathology of the human lesion. The first focus of the SCOR is in tests of the major current theories of the origin of plaque smooth muscle cells. The possibility that plaques begin with a viral mutagenic event is studied by a systematic search for plaque viri and study of the virology of vessel wall cells. The possibility that plaques originate developmentally is explored by an attempt at cloning genes whose expression is unique to the atherosclerotic plaque. Monoclonality of the lesion is studied at a new level using X- linked RNA polymorphisms to determine when and how monoclonality arises. The possibility that plaques originate as an inflammatory process is examined by looking at the role of plaque macrophages in expressing growth factors. All of these studies are carried out in human tissue. Tests of the hypotheses will depend on our ability to demonstrate the expected results in the human lesion. The second area of focus, studies of plaque progression, also emphasize the study of inflammatory mechanisms in the human lesion. Two projects include studies of the control of cytokine production by plaque macrophages and control of expression of leukocyte adhesion molecules. In addition to studies of the inflammatory process, one project is directed at lipoprotein lipase. The plaque macrophage, as well as the smooth muscle cell, are both studied as sources of lipoprotein lipase, an enzyme necessary to form free fatty acids. The project examines the control of expression of this enzyme by lineage-specific-cis-acting elements and elements responding to hormone factors. Finally, the SCOR proposes a new and unique approach to therapy of plaque pro-coagulant events by proposing use of a recombinant form of annexin, a phosphotidyl-serine binding protein, as an anticoagulant able to localize at sites of thrombosis.