Oxidized Phospholipids and Angiogenesis

描述 （申请人的摘要）Karol沃森博士是一位医生/科学家， 在动脉粥样硬化和血管生成方面的研究背景， 结合这两个领域的研究计划。 她的长期职业目标 成为一个富有成效的，独立的调查员在该领域的 动脉粥样硬化相关的血管生成。 由于快速发展， 血管生成和动脉粥样硬化的领域 培训和职业发展对她的未来至关重要。 的 环境：加州大学洛杉矶分校的环境是这个职业发展的理想选择。 沃森博士已经得到保证，受保护的研究时间，这将使她能够 她80%的时间用于研究，拥有设备齐全的实验室， 她导师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， 毛细血管是从现有的微血管生成的。 许多 已经鉴定出调节血管生成的蛋白质，并且在过去的几年中， 多年来，脂质介质也被研究。 它是对潜能的研究 血管生成的脂质介质（即氧化磷脂介质）， 这是目前提案的基础。 低密度脂蛋白（LDL）- 衍生的氧化磷脂在动脉粥样硬化的发展中是重要的， 硬化症 该实验室的新证据表明， 氧化磷脂也可以作为血管生成的介质。 主要 本提案的目的是阐明这些脂质氧化的作用， 产品在体内刺激血管生成，并研究的作用， 单核细胞/巨噬细胞在这个过程中。 这项资助的总体假设是 脂质氧化产物通过以下方式诱导体内血管生成：a）吸引 和B）刺激单核细胞/巨噬细胞以产生 有效的血管生成因子如VEGF。 为了解决这个假设， 确定了以下具体目标：1）确定 单核细胞/巨噬细胞产物对体外血管生成的影响 氧化磷脂 2)为了检验全身脂质 氧化产物导致单核细胞/巨噬细胞上调VEGF分泌 并刺激体内血管生成。 3)为了验证这个假设， 巨噬细胞是氧化磷脂诱导的血管生成所必需的， 在巨噬细胞缺陷小鼠中进行血管生成测定。 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，并可能解释的共同- 动脉粥样硬化和体内血管生成的定位。

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.