Oxidized Phospholipids and Angiogenesis

氧化磷脂和血管生成

• 批准号: 6627723
• 负责人: KAROL E WATSON
• 金额: $ 12.72万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6627723
• 关键词: angiogenesis; atherosclerosis; laboratory mouse; low density lipoprotein; macrophage; monocyte; oxidized lipid; phospholipids; tissue /cell culture; vascular endothelial growth factors

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.

描述 （申请人的摘要）Karol Watson博士是一位医师/科学家 正在发展的动脉粥样硬化和血管生成的研究背景 结合了两个领域的研究计划。 她的长期职业目标 成为一名富有成效的独立研究者 动脉粥样硬化与血管生成有关。 因为 血管生成和动脉粥样硬化的田地其他研究 培训和职业发展对于她的未来至关重要。 这 环境：加州大学洛杉矶分校的环境是这一职业发展的理想选择。 沃森博士得到了保证，受保护的研究时间，这将使她能够 将她的80％的时间用于研究，一个设备齐全的实验室和进入 她的导师实验室中的所有设备和专业知识以及 顾问。 研究：血管生成是复杂的过程 毛细血管是由现有微血管产生的。 许多 调节血管生成的蛋白质已被鉴定出来，并且在过去的几个 多年来，还研究了脂质介质。 这是对潜力的研究 血管生成的脂质介质（即氧化的磷脂介质） 构成当前建议的基础。 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很重要 硬化。 该实验室的新兴证据表明这些 氧化的磷脂也可以充当血管生成的介体。 专业 该提案的目标是阐明这些脂质氧化的作用 刺激体内血管生成的产物，并研究 在此过程中的单核细胞/巨噬细胞。 这笔赠款的总体假设是 脂质氧化产物在体内诱导血管生成：a）吸引 单核细胞/巨噬细胞，b）刺激单核细胞/巨噬细胞产生 有效的血管生成因子，例如VEGF。 为了解决这个假设 已经建立了以下具体目标：1）确定 在存在的情况下，单核细胞/巨噬细胞产物在体外血管生成上 氧化的磷脂。 2）测试全身性脂质的假设 氧化产物导致单核细胞/巨噬细胞上调VEGF的分泌 并在体内刺激血管生成。 3）检验以下假设 巨噬细胞对于氧化的磷脂诱导的血管生成是必需的 在巨噬细胞缺陷的小鼠中进行血管生成测定。 信息 这些实验得出的将有助于理解 血管生成中的脂质氧化产物，并有可能解释共同生成 动脉粥样硬化和血管生成的定位。