GENE EXPRESSION OF GIANT CELL ARTERITIS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。目前尚不确定特定血管部位的选择性损伤是由于免疫功能的原发异常，还是最初出现在曾经正常的血管内引发免疫炎症反应的异常。以往评价巨细胞动脉(GCA)发病机制的研究主要集中在对血管壁内炎症事件的描述。然而，为什么会发生选择性血管靶向，或者是什么获得性血管改变会导致特定血管的疾病，这一问题还没有得到解决。靶器官固有的结构和功能特性也可能导致组织损伤的发生和不同的临床表型，以确定在老年人GCA中获得性血管壁异常是否先于炎性损伤(空洞)并且是炎性损伤所必需的。假设：GCA的选择性器官靶向是由血管壁的变化触发的，其中可能包括改变的基因或蛋白质谱。这种变化可能有内生或外生的根源。如果系统地检查炎症动脉的完整节段，并与年龄和性别匹配的正常对照血管进行比较，独特的基因组模式可能识别GCA发病机制中的初始事件。GCA中影响血管壁的炎症过程往往是不连续的。我们推测，与炎症损伤区域相邻的明显正常的颞动脉节段，即所谓的跳跃性病变，将揭示血管壁最初的异常，从而引发损伤性反应。在这项研究中，我们建议使用微阵列技术专门研究经活检证实的GCA患者的颞动脉跳跃性病变的基因表达模式的变异，并将它们与年龄、性别和种族匹配的对照组进行比较。具体目的：1.确定GCA影响颞动脉跳跃性病变的基因表达模式。将GCA中的颞动脉的基因图谱与年龄、性别和种族相匹配的对照标本进行比较，以确定不同的血管底物指纹，这些指纹可能是驱动炎症损伤的最初SEP。2.应用实时荧光定量聚合酶链式反应技术，以独立方法验证特定目的1的基因芯片分析所获得的数据。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. It is uncertain whether selective injury to specific vascular sites is due to primary abnormalities of immune function or abnormalities that first appear within the once normal vessel that ¿invited¿ an immuno-inflammatory response. Prior studies, that have evaluated the pathogenesis of giant cell arteries, (GCA) have focused mostly on description of the inflammatory events within the vessel wall. However, the question of why selective vessel targeting occurs or what acquired vessel changes lead to triggering disease in specific vessels has not been addressed. Inherent structural and functional properties of the target organ may also contribute to the development of tissue damage and different clinical phenotype to determine whether acquired abnormalities within the vessel wall precede and are required for inflammatory injury (vacuities) in GCA of the elderly. Hypothesis: Selective organ targeting in GCA is triggered by changes in the vessel wall that may include altered gene or protein profiles. Such changes may have endogenous or exogenous origins. If intact segments of inflamed arteries are systematically examined and compared to age and gender matched normal control vessels, unique genomic patterns may identify the initial events in the pathogenesis of GCA. The inflammatory process affecting the vessel wall in GCA is often discontinuous. We are presuming that apparently normal segments of temporal artery, referred to as ¿skip lesions¿, that are adjacent to areas damaged by inflammation, will reveal initial abnormalities in the vessel wall that ¿invite¿ an injurious reaction. In this study, we propose to use microarray techniques to specifically investigate variations in gene expression patters of ¿skip lesions¿ of temporal arteries from patients with biopsy-proven GCA and compare them to age, gender and ethnicity matched controls. Specific Aims: 1. Identify gene expression patters of ¿skip lesions¿ in temporal arteries affected by GCA. Compare gene profiles of temporal arteries in GCA to control specimens, matched for age, gender and ethnicity to identify distinct vessel substrate fingerprints that may be the initial sep in driving inflammatory injury. 2. To validate the data obtained from microarray analysis in specific aim 1 by independent approach using Real Time Quantitative PCR technique.