CYTOKINE REGULATION OF CHOLESTEROL TRAFFICKING

动脉粥样硬化是美国发病率和死亡率的主要原因。 各州。血浆低密度脂蛋白和胆固醇水平是高血压的主要危险因素 发展。在人类中，肝脏主要控制血浆低密度脂蛋白和 低密度脂蛋白受体介导的分解代谢和胆固醇水平 胆固醇/脂蛋白的生物合成。动脉粥样硬化的环境 富含细胞因子和生长因子的斑块可能是 揭开和控制动脉粥样硬化。这项研究的目标是 该项目是在细胞和分子水平上定义 微环境衍生的可溶性介质对受体依赖性的调节 和胆固醇的独立摄取、合成和积累 肝母细胞瘤来源的细胞中的血管壁以及系统 排队。功能活性和基因表达调控机制的研究进展 低密度脂蛋白受体、清道夫受体和HMG-CoA还原酶将 在构成动脉粥样硬化斑块的细胞中定义并相关 伴随着SMC和巨噬细胞胆固醇的积聚。关键的调解人 血管胆固醇运输将被比作炎症性和 血管细胞衍生细胞因子对肝脏胆固醇代谢的调节。 理解并最终协调血管细胞胆固醇 生理学和肝脏胆固醇分解代谢是长期目标。

Atherosclerosis is the major cause of morbidity and mortality in the United States. Plasma levels of LDL and cholesterol are major risk factors to its development. In humans, the liver primarily controls plasma LDL and cholesterol levels through LDL receptor-mediated catabolism and cholesterol/lipoprotein biosynthesis. The milieu of the atherosclerotic plaque, enriched with cytokines and growth factors, may be the key to unravelling and controlling atherosclerosis. The goals of this research project are to define at the cellular and molecular level the role of microenvironment derived soluble mediators in regulating receptor-dependent and independent uptake, synthesis, and accumulation of cholesterol at the vessel wall, as well as systemically, in a hepatoblastoma-derived cell line. The mechanisms regulating functional activity and gene expression of the LDL receptor, scavenger receptor, and HMG-CoA reductase enzyme will be defined in the cells comprising the atherosclerotic plaque and correlated with SMC and macrophage cholesterol accumulation. Key mediators of vascular cholesterol trafficking will be compared to inflammatory and vascular cell-derived cytokine regulation of liver cholesterol metabolism. Understanding, and thus ultimately coordinating vascular cell cholesterol physiology with liver cholesterol catabolism is the long-term aim.