Oxidized Phospholipids and Angiogenesis

描述 (申请者摘要)卡罗尔·沃森博士是一位内科医生/科学家 动脉粥样硬化和血管生成的研究背景谁在发展中 一个结合了这两个领域的研究项目。她的长期职业目标 将成为一名富有成效的独立调查者 动脉粥样硬化与血管生成相关。因为在中国的快速发展 血管生成和动脉粥样硬化领域的补充研究 培训和职业发展对她的未来至关重要。这个 环境：加州大学洛杉矶分校的环境非常适合这一职业发展。 沃森博士已得到保证，受保护的研究时间将使她能够 她80%的时间都花在研究上，一个设备齐全的实验室和 她导师和她实验室里的所有设备和专业知识 顾问。研究：血管生成是一个复杂的过程，新的 毛细血管是由现有的微血管生成的。许多 调节血管生成的蛋白质已经被识别出来，在过去的几年里 多年来，人们也一直在研究脂质介体。它是对潜力的研究 血管生成的脂质介质(即氧化型磷脂介质) 构成了当前提案的基础。低密度脂蛋白(LDL)- 衍生氧化磷脂在动脉粥样硬化的发展中起着重要作用。 硬化症。来自该实验室的新证据表明，这些 氧化磷脂也可能作为血管生成的介体。少校 这项建议的目的是阐明这些脂质氧化的作用。 在刺激体内血管生成方面，并探讨其作用 单核/巨噬细胞在这一过程中。这笔赠款的总体假设是 体内脂质氧化产物通过：a)吸引诱导血管生成 单核/巨噬细胞，以及b)刺激单核/巨噬细胞产生 强大的血管生成因子，如血管内皮生长因子。为了解决这一假设，以下是 已经确定了以下具体目标：1)确定 单核/巨噬细胞产物对体外血管生成的影响 氧化磷脂。2)检验假设全身性脂质 氧化产物导致单核/巨噬细胞上调血管内皮生长因子的分泌 并刺激体内血管生成。3)检验假设 巨噬细胞是氧化磷脂诱导血管生成所必需的 对巨噬细胞缺陷小鼠进行血管生成检测。信息 从这些实验中得出的结论将有助于理解 脂质氧化产物在血管生成中的作用，并潜在地解释了 动脉粥样硬化和血管生成的体内定位。

DESCRIPTION (Applicant's abstract) Dr. Karol Watson is a physician/scientist with a research background in both atherosclerosis and angiogenesis who is developing a research program that combines the two fields. Her long-term career goals are to become a productive, independent investigator in the field of atherosclerosis associated angiogenesis. Because of the rapid developments in the fields of both angiogenesis and atherosclerosis additional research training and career development will be essential to her future. The Environment: The environment at UCLA is ideal for this career development. Dr. Watson has been assured, protected research time that will allow her to spend 80% of her time in research, a fully equipped laboratory and access to all of the equipment and expertise in the laboratories of her mentors and advisors. The Research: Angiogenesis is the complex process by which new capillary blood vessels are generated from existing microvessels. Many proteins which modulate angiogenesis have been identified, and in the past few years, lipid mediators have also been studied. It is the study of potential lipid mediators of angiogenesis (namely oxidized phospholipid mediators) which forms the basis for the current proposal. Low density lipoprotein (LDL)- derived oxidized phospholipids are important in the development of athero- sclerosis. Emerging evidence from this laboratory suggests that these oxidized phospholipids may also act as mediators of angiogenesis. The major objectives of this proposal are to clarify the role of these lipid oxidation products in stimulating angiogenesis in vivo, and to investigate the role of monocyte/macrophages in the process. The overall hypothesis of this grant is that lipid oxidation products induce angiogenesis in vivo via: a) attraction of monocyte/macrophages, and b) stimulation of monocyte/macrophages to produce potent angiogenic factors such as VEGF. To address this hypothesis this following specific aims have been established: 1) To determine the effects of monocyte/macrophage products on in vitro angiogenesis in the presence of oxidized phospholipids. 2) To test the hypothesis that systemic lipid oxidation products cause monocyte/macrophages to upregulate secretion of VEGF and stimulate angiogenesis in vivo. 3) To test the hypothesis that macrophages are necessary for oxidized phospholipid-induced angiogenesis by performing angiogenesis assays in macrophage-deficient mice. Information derived from these experiments will contribute to understanding the role of lipid oxidation products in angiogenesis, and potentially explain the co- localization of atherosclerosis and angiogenesis in vivo.