Small Lucine-Rich Proteoglycans and Atherogenesis

描述(由申请人提供)： SCOR提出了一套综合的基础和临床研究，旨在 在动脉水平确定动脉粥样硬化形成的分子机制 墙。动脉壁酶、脂蛋白和脂蛋白在动脉粥样硬化形成中的作用 蛋白多糖将在转基因小鼠模型和细胞中进行研究 文化。在人类身上进行的一系列平行研究将确定 在小鼠和细胞培养中定义的机制与 人类动脉粥样硬化的病理生理学。因此，SCOR将定义新的 动脉粥样硬化形成机制及评价其在人类中的意义。 项目6(TALL)将评估动脉粥样硬化泡沫细胞退化的机制 这是高密度脂蛋白或其载脂蛋白与巨噬细胞相互作用的结果 ABCA1.项目1(TABAS)将研究动脉壁的作用 鞘磷脂酶在脂蛋白滞留和聚集及巨噬细胞泡沫中的作用 细胞形成。项目7(威廉姆斯)将评估动脉壁的作用 蛋白多糖在脂蛋白滞留中的作用，并将研究其作用机制和 最近发现的核心蛋白多糖缺陷小鼠的意义 动脉粥样硬化形成加速。项目8(Goldberg)将研究 在动脉粥样硬化形成中的作用，并将确定这种蛋白多糖在 防止致动脉粥样硬化的脂蛋白穿透动脉壁。 四个核心将是A)行政；B)临床/生物统计学；Q基因 表情分析；D)病理学。《公约》的主要主题是 研究血浆脂蛋白与蛋白多糖的相互作用， 动脉壁的酶和细胞，并确定分子机制 促进或改善动脉粥样硬化泡沫细胞的形成。这些研究是 可能揭示关于特定动脉壁作用的新信息 小鼠和人类动脉粥样硬化中的分子，导致诊断的改进 以及这种疾病的治疗。

DESCRIPTION (provided by the applicant): The SCOR proposes an integrated set of basic and clinical studies aiming to define molecular mechanisms of atherogenesis at the level of the arterial wall. Effects on atherogenesis of arterial wall enzymes, lipoproteins and proteoglycans will be investigated in transgenic mouse models and in cell culture. A parallel set of investigations in humans will determine the relevance of mechanisms defined in mice and in cell culture to the pathophysiology of human atherosclerosis. Thus, the SCOR will define new mechanisms of atherogenesis and evaluate their significance in humans. Project 6 (Tall) will evaluate the mechanisms of atheroma foam cell regression that result from the interaction of HDL or its apolipoproteins with macrophage ABCA1. Project 1 (Tabas) will investigate the role of arterial wall sphingomyelinase in lipoprotein retention and aggregation, and macrophage foam cell formation. Project 7 (Williams) will evaluate the role of arterial wall proteoglycans in lipoprotein retention, and will study the mechanisms and significance of the recent finding that mice deficient in decorin proteoglycan have acclerated atherogenesis. Project 8 (Goldberg) will study the role of perlecan in atherogenesis, and will determine the role of this proteoglycan in preventing penetration of atherogenic lipoproteins into the arterial wall. The four cores will be A) Administrative; B) Clinical/Biostatistics; Q Gene Expression Profiling; and D) Pathology. The major theme of the SCOR is to investigate the interactions of plasma lipoproteins with proteoglycans, enzymes and cells of the arterial wall, and to define molecular mechanisms that promote or ameliorate atheroma foam cell formation. The studies are likely to reveal novel information about the role of specific arterial wall molecules in atherosclerosis in mice and humans, leading to improved diagnosis and treatment of this disease.