CYTOKINE REGULATION OF CHOLESTEROL TRAFFICKING

在美国，动脉粥样硬化是发病率和死亡率的主要原因。 States. 血浆低密度脂蛋白和胆固醇水平是其主要危险因素， 发展 在人类中，肝脏主要控制血浆LDL， 胆固醇水平通过LDL受体介导的catalysis和 胆固醇/脂蛋白生物合成。 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 解开和控制动脉粥样硬化。 这项研究的目的是 项目是在细胞和分子水平上定义 微环境来源的可溶性介质调节受体依赖性 和独立的摄取，合成和积累的胆固醇在 血管壁，以及全身，在肝母细胞瘤衍生细胞 线 调节功能活性和基因表达的机制 LDL受体、清道夫受体和HMG-CoA还原酶将被 在包含动脉粥样硬化斑块的细胞中定义， SMC和巨噬细胞胆固醇积聚。 的关键介质 血管胆固醇运输将与炎症和 血管细胞衍生的细胞因子调节肝脏胆固醇代谢。 了解并最终协调血管细胞胆固醇 长期目标是改善肝脏胆固醇代谢。

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.