Signature Protein Profiles to Identify AAAs

腹主动脉瘤(Aaa)被定义为肾下主动脉的病理性扩张。 常伴有明显的动脉粥样硬化、炎症和血栓形成。而AAA则是 这种疾病很常见，而且往往是致命的，其潜在的形成机制尚不清楚。同样重要的是， 没有足够的手段来快速分层动脉瘤的发展、进展或最终的风险， 破裂。我们假设AAA产生独特的蛋白质特征图谱，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，通过对血清的询问， 定制的蛋白质微阵列，我们预计我们将识别独特的血管衍生蛋白质模式， 将作为AAA发展的敏感和特异标记物。此外，还可以监测蛋白质图谱 用于预测动脉瘤扩大以及对治疗的反应。因此，我们建议解决 以下是具体目标： 特异性目的1：研制一种同时提供丰度的抗体平面阵列 测量大约50个炎症和蛋白水解酶活性的血清标志物。 特异性目的2：进行一项血清标记物研究，比较AAA患者和匹配的对照组 确定与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，以确定动脉瘤的预测因素 进步。 特异目的4：测定AAA和AAA患者积极干预后的蛋白质谱 确定是否可以确定对治疗的有益反应。

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.