LIPOPROTEIN/GENETIC MODIFICATION AND ADHESION MOLECULES

脂蛋白/基因修饰和粘附分子

• 批准号: 2027036
• 负责人: Bobby Khan
• 金额: $ 8.37万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-04-01 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2027036
• 关键词: atherosclerosis; cell adhesion molecules; cytokine; enzyme linked immunosorbent assay; flow cytometry; gene expression; genetic regulation; human fetus tissue; low density lipoprotein; molecular pathology; northern blottings; oxidation reduction reaction; oxidative stress; selectins; tissue /cell culture; transcription factor; tumor necrosis factor alpha; vascular endothelium

Oxidative stress and expression of the vascular cell adhesion molecule-1 (VCAM-1) on vascular endothelial cells are early features in the pathogenesis of atherosclerosis and other inflammatory diseases. We have recently demonstrated a linkage between oxidation-reduction (redox) sensitive regulatory mechanisms and the expression of vascular endothelial cell genes, such as VCAM-1, that are involved in the early inflammatory processes characteristic of atherosclerosis. To explore the molecular determinants of atherogenesis, this proposal will characterize the molecular regulatory mechanisms through which modified low density lipoprotein (LDL) regulates VCAM-1 gene expression in human vascular endothelial cells and to identify the specific oxidation-reduction sensitive transcriptional regulatory factor(s) that mediate this effect. Using an integrated immunological, biochemical, cellular, and molecular biological approach in cultured human vascular endothelial cells, the regulatory effects of modified LDLs, both oxidized and glycated, as primary regulators and as modulators of cytokine activation of VCAM-1, ICAM-1, and E-selectin will be defined. This combined approach will be used to define the specific oxidant compounds within modified LDL that regulate VCAM-1 expression. Using these defined oxidants, an in vitro "knockout" approach is proposed, using synthetic oligonucleotides, to define the role of specific, endogenously expressed transcriptional regulatory factor(s) in the regulation of endogenous VCAM-1 gene expression.

氧化应激与血管细胞粘附分子-1的表达