Interaction of Macrophages with Marix-Associated Lipoproteins

巨噬细胞与 Marix 相关脂蛋白的相互作用

• 批准号: 7226033
• 负责人: ABIGAIL Susan HAKA
• 金额: $ 4.88万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-15 至 2009-07-11
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7226033
• 关键词: Adopted; Affect; Animal Model; Animals; Area; Arterial Fatty Streak; Atherosclerosis; Behavior; Binding; Biology; Cell Culture System; Cell membrane; Cells; Cellular Morphology; Cholesterol; Cholesterol Esters; Condition; Disease regression; Environment; Event; Extracellular Matrix; Fellowship; Foam Cells; Goals; In Vitro; Incubated; Individual; Knowledge; Lead; Lesion; Light; Lipids; Lipoprotein Binding; Lipoproteins; Low-Density Lipoproteins; Membrane; Mesentery; Methods; Monitor; Morphology; Names; Physiological; Process; Purpose; System; Time; Tissue Model; atherogenesis; cholesterol analog; design; experience; fluorescence imaging; in vivo; innovation; insight; intravital microscopy; macrophage; migration; monocyte; particle; physiologic model; tissue culture

DESCRIPTION (provided by applicant): The studies proposed herein will provide new insights into the early steps of atherogenesis. We hypothesize that as macrophages come into contact with matrix-retained LDL aggregates, rapid cholesterol ester transfer occurs. This results in an increase in macrophage membrane cholesterol levels and changes in cell morphology and migratory ability. This process may explain why macrophages within atherosclerotic lesions continue to take up retained lipoproteins and develop into nonmotile foam cells. To investigate this hypothesis, time-lapse confocal fluorescence imaging of in vitro tissue cultures will be utilized to examine macrophage morphological alterations induced during their initial contact with matrix-associated lipoproteins. Further, monitoring the transfer of a fluorescent cholesterol analog from LDL to macrophages allows direct observation of changes in plasma membrane cholesterol levels. Finally, studies will extend our observations on in vitro tissue models to in vivo examination of macrophage migratory behavior in animal models of atherosclerosis. Intravital microscopy will be used for quantification of monocyte/macrophage diapedesis. Results may eventually lead to innovative methods of promoting atherosclerotic lesion regression.

描述（由申请人提供）：本文提出的研究将为动脉粥样硬化形成的早期步骤提供新的见解。我们推测，当巨噬细胞与基质保留的LDL聚集体接触时，会发生快速的胆固醇酯转移。这导致巨噬细胞膜胆固醇水平增加以及细胞形态和迁移能力的变化。这一过程可以解释为什么动脉粥样硬化病变内的巨噬细胞继续摄取残留的脂蛋白并发育成非运动性泡沫细胞。为了研究这一假设，将利用体外组织培养物的延时共聚焦荧光成像来检查巨噬细胞在与基质相关脂蛋白的初始接触期间诱导的形态学改变。此外，监测荧光胆固醇类似物从LDL到巨噬细胞的转移允许直接观察质膜胆固醇水平的变化。最后，研究将扩大我们在体外组织模型的观察，在动脉粥样硬化动物模型中的巨噬细胞迁移行为的体内检查。将使用活体显微镜定量单核细胞/巨噬细胞渗出。结果可能最终导致促进动脉粥样硬化病变消退的创新方法。