SCOR IN ARTERIOSCLEROSIS

这是一份申请书，申请成立一个新的SCOR项目， 人类动脉粥样硬化。 该提案包括六个项目， 病理科、血液科、检验科、生化科、 和遗传学。 每一个都围绕着测试一个特定的现有的 试图解释动脉粥样硬化病变起源的假说 或这些病变进展为临床上显著的，终身的- 威胁血管阻塞 这些项目由一个 致力于人类病变病理学的核心实验室。 SCOR的第一个重点是测试当前的主要理论 斑块平滑肌细胞的起源。 斑块有可能 通过系统检索研究病毒致突变事件的开始， 空斑病毒和血管壁细胞病毒学的研究。 的 斑块起源于发育的可能性是由一个 试图克隆动脉粥样硬化特有表达的基因， 斑块 单克隆性的病变研究在一个新的水平，使用X- 连锁的RNA多态性，以确定何时以及如何单克隆性出现。 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查， 因素 所有这些研究都在人体组织中进行。 试验 这些假设将取决于我们证明预期结果的能力。 导致人体病变。 第二个重点领域，斑块进展的研究，也强调 研究人类病变的炎症机制。 两个项目包括 噬斑巨噬细胞控制细胞因子产生的研究， 控制白细胞粘附分子的表达。 除了 炎症过程的研究，一个项目是针对脂蛋白 脂肪酶 斑块巨噬细胞以及平滑肌细胞都是 作为脂蛋白脂肪酶的来源，脂蛋白脂肪酶是形成游离脂肪酸所必需的酶。 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响应激素的元件 因素 最后，SCOR提出了一种新的和独特的方法来治疗斑块 促凝血事件，建议使用重组形式的膜联蛋白， 磷脂酰丝氨酸结合蛋白，作为抗凝剂能够定位 在血栓形成的部位。

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.