Signature Protein Profiles to Identify AAAs

用于识别 AAA 的特征蛋白谱

• 批准号: 7140916
• 负责人: Philip S Tsao
• 金额: $ 19.31万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7140916
• 关键词: abdomen; aorta aneurysm; biomarker; cardiovascular disorder diagnosis; cardiovascular disorder epidemiology; cardiovascular disorder therapy; endopeptidases; enzyme activity; human subject; human therapy evaluation; inflammation; longitudinal human study; microarray technology; pathologic process; patient oriented research; protein structure function; technology /technique development

An abdominal aortic aneurysm (AAA) is defined as a pathologic dilatation of the infrarenal aorta that is often accompanied by significant superimposed atherosclerosis, inflammation and thrombosis. While AAAs are common and often lethal, the underlying mechanisms of formation are not well understood. Equally important, there are not adequate means to rapidly stratify risk of aneurysm development, progression, or ultimately, rupture. We hypothesize that AAAs produce unique signature profiles of proteins that include aspects of inflammation, apoptosis, extracellular matrix breakdown and thrombosis. Thus, by interrogation of serum with custom protein microarrays, we anticipate that we will identify unique patterns of vascular-derived proteins that will serve as sensitive and specific markers of AAA development. In addition, protein profiles can be monitored for prediction of aneurysm expansion as well as response to therapy. Therefore, we propose to address the following specific aims: SPECIFIC AIM 1: To develop an antibody-based planar array providing simultaneous abundance measurements for approximately 50 serum markers of inflammation and protease activity. SPECIFIC AIM 2: To conduct a serum marker study comparing cases with AAA and matched controls to identify protein patterns that correlate with AAA formation. SPECIFIC AIM 3: To conduct a longitudinal prospective study in cases to identify predictors of aneurvsm progression. SPECIFIC AIM 4: To determine protein profiles in patients undergoing active intervention for AAA and determine if beneficial response to therapy can be ascertained.

腹主动脉瘤（AAA）定义为肾下主动脉的病理性扩张， 通常伴有明显的叠加动脉粥样硬化、炎症和血栓形成。虽然AAA 常见的，往往是致命的，形成的基本机制还没有很好地理解。同样重要的是， 没有足够的方法来快速地对动脉瘤发展、进展的风险进行分层，或者最终， 破裂我们假设AAAs产生独特的蛋白质特征谱，包括以下方面： 炎症、细胞凋亡、细胞外基质分解和血栓形成。因此，通过询问血清， 定制的蛋白质微阵列，我们预计，我们将确定独特的模式，血管来源的蛋白质， 将作为AAA发展的敏感和特异性标志物。此外，还可以监测蛋白质谱 用于预测动脉瘤扩张以及对治疗的反应。因此，我们建议处理 具体目标如下： 具体目标1：开发一种基于抗体的平面阵列， 测量大约50种炎症和蛋白酶活性的血清标志物。 具体目的2：进行一项血清标志物研究，比较AAA病例和匹配对照， 鉴定与AAA形成相关的蛋白质模式。 具体目标3：在病例中进行纵向前瞻性研究，以确定BVsm的预测因子 进展 特定目的4：确定接受主动介入治疗AAA的患者的蛋白质谱， 确定是否可以确定对治疗的有益反应。