Gene expression in cardiovascular disease

心血管疾病中的基因表达

• 批准号: 6682628
• 负责人: JOSEPH R NEVINS
• 金额: $ 36.34万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6682628
• 关键词: age difference; aorta; atherosclerosis; gene expression; genetic mapping; genetic polymorphism; genetic susceptibility; human tissue; microarray technology; pathologic process; proteomics; serial analysis of gene expression

The goal of Component I is to develop the methodologies and approaches to identification of genes that contribute to cardiovascular disease. We propose to use various measures of gene expression, employing DNA microarrays, SAGE , and protein analysis, to develop experimental approaches to the molecular characterization of atherosclerosis in the aorta. Specifically, we will take a variety of approaches to the determination of gene expression changes that characterize the advance of atherosclerosis in vascular tissue. The overarching goal is to utilize large scale analysis of gene expression to identify patterns that reflect the stages of vascular disease progression. Our work will focus on the analysis of aorta derived from transplant donors that are separated into three groupings based on age: The tissue samples will be analyzed at the time of removal from the presence of vascular disease. We propose to utilize both SAGE and DNA microarray analysis to identify patterns of expression that reflect disease phenotype and then use this information to identify genes that may contribute to cardiovascular disease process. We will also employ proteomics to identify proteins that are specifically modified in these same tissues. This will serve as the basis for the identification of genes that contribute to the disease process and in which polymorphic variations may contribute to the disease process. The gene expression data generated in this component, analyzed by the statistical methodologies detailed in component 4, will yield prioritized gene lists that will feed into the activities of Component 2 for the discovery of polymorphic gene variants. To accomplish these goals we will focus our attention on the collection of vascular tissue from organ transplant donors, that have been characterized with respect to disease progression, to enable the gene expression and protein analyses. We will utilize a variety of complementary technologies for the generation of this data and to then allow a determination of the original approach to the identification of genes that contribute to the disease process.

构成部分一的目标是开发识别导致心血管疾病的基因的方法和途径。我们建议使用不同的基因表达测量方法，使用DNA微阵列、SAGE和蛋白质分析，来开发实验方法来表征动脉粥样硬化的分子特征。具体地说，我们将采取多种方法来确定表征动脉粥样硬化进展的血管组织中的基因表达变化。首要目标是利用大规模的基因表达分析来确定反映血管疾病进展阶段的模式。我们的工作将集中于对来自移植供者的主动脉进行分析，根据年龄分为三组：组织样本将在切除时进行分析，以确定是否存在血管疾病。我们建议利用SAGE和DNA微阵列分析来识别反映疾病表型的表达模式，然后使用这些信息来识别可能与心血管疾病过程有关的基因。我们还将使用蛋白质组学来识别在这些相同组织中特定修饰的蛋白质。这将作为识别促进疾病过程的基因以及多态变异可能有助于疾病过程的基因的基础。这一组成部分产生的基因表达数据，通过组成部分4中详细介绍的统计方法进行分析，将产生优先基因清单，这些清单将提供给组成部分2的活动，以发现多态基因变异。 为了实现这些目标，我们将把注意力集中在从器官移植捐赠者那里收集血管组织，这些组织已经被描述为疾病进展的特征，以便能够进行基因表达和蛋白质分析。我们将利用各种补充技术来生成这些数据，然后确定识别导致疾病过程的基因的原始方法。