Gene expression in cardiovascular disease

第一部分的目标是开发方法和途径来鉴定导致心血管疾病的基因。我们建议使用各种措施的基因表达，采用DNA微阵列，SAGE，和蛋白质分析，开发实验方法的分子表征动脉粥样硬化的主动脉。具体来说，我们将采取各种方法来确定血管组织中动脉粥样硬化进展的基因表达变化。总体目标是利用大规模的基因表达分析，以确定反映血管疾病进展阶段的模式。我们的工作将集中在分析来自移植供体的主动脉，这些供体根据年龄分为三组：组织样本将在从存在血管疾病的组织中取出时进行分析。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有助于心血管疾病过程的基因。我们还将采用蛋白质组学来鉴定在这些相同组织中特异性修饰的蛋白质。这将作为基础，用于识别基因，有助于疾病的过程中，多态性变异可能有助于疾病的过程。在该组件中生成的基因表达数据，通过组件4中详述的统计方法进行分析，将产生优先化的基因列表，这些基因列表将输入组件2的活动，用于发现多态性基因变体。 为了实现这些目标，我们将把注意力集中在从器官移植供体收集血管组织上，这些组织已经被表征为疾病进展，以使基因表达和蛋白质分析成为可能。我们将利用各种互补技术来生成这些数据，然后确定用于识别导致疾病过程的基因的原始方法。

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.