Signature Protein Profiles to Identify Disease Progression and Therapeutic Modification in Murine and Human Models of Aortic Abdominal Aneurysms

用于识别小鼠和人类腹主动脉瘤模型中疾病进展和治疗修改的特征蛋白谱

• 批准号: 115077029
• 负责人: Professor Dr. Lars Mägdefessel
• 金额: --
• 依托单位: Division of Cardiovascular Medicine
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/115077029?language=en
• 关键词: Signature; Protein; Profiles; Identify; Disease

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. My hypothesis is 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, I anticipate that we will identify unique patterns of vascular-derived proteins that will serve as sensitive and specific markers of AAA development. AAAs produce and secrete specific proteins during the natural course of disease that can be interrogated in serum. The expression pattern of a mix of these proteins will be more sensitive and specific for AAA than any single protein. In addition, protein profiles can be monitored for prediction of aneurysm expansion as well as response to new therapeutical approaches like matrix-metalloproteinase-inhibitors, activators of collagen synthesis, and anti-inflammatory effects of statins. We propose to build an antibody microarray based on the previous work done at Stanford University profiling inflammatory proteins associated with atherosclerosis and supplementing this list with proteins identified by transcriptional profiling of tissue derived from human AAAs as well as predictive murine models.

腹主动脉瘤(AAA)定义为肾下主动脉病理性扩张，常伴有显著的动脉粥样硬化、炎症和血栓形成。虽然AAA很常见，而且往往是致命的，但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、进展或最终破裂的风险。我的假设是，AAA产生独特的蛋白质特征图谱，包括炎症、凋亡、细胞外基质分解和血栓形成等方面。因此，通过使用定制的蛋白质微阵列询问血清，我预计我们将识别独特的血管衍生蛋白质模式，这些蛋白质将作为AAA发展的敏感和特异的标记。AAAS在疾病的自然过程中产生和分泌特定的蛋白质，可以在血清中进行检测。这些蛋白的混合表达模式对AAA比任何单一蛋白都更敏感和特异。此外，可以监测蛋白质谱来预测动脉瘤的扩大以及对新的治疗方法的反应，如基质金属蛋白酶抑制剂、胶原合成激活剂和他汀类药物的抗炎作用。我们建议在斯坦福大学之前所做工作的基础上建立一个抗体微阵列，分析与动脉粥样硬化相关的炎性蛋白，并用来自人AAA和预测小鼠模型的组织的转录表达谱鉴定的蛋白质来补充这个列表。