AAA Disease: Mechanism, Stratification and Treatment

AAA 疾病：机制、分层和治疗

• 批准号: 7425376
• 负责人: RONALD L DALMAN
• 金额: $ 237.34万
• 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: 2006-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7425376
• 关键词: AAA; Disease; Mechanism; Stratification; Treatment

DESCRIPTION (provided by applicant): Abdominal aortic aneurysm (AAA) is a common, morbid, and frequently lethal disease of older Americans. Major clinical challenges in AAA disease include the absence of: 1) effective non-surgical therapies to prevent progression of early stage disease, and 2) validated biomarkers or efficient imaging indices to monitor disease activity and guide suppressive medical therapies in small aneurysms. Based on extensive prior evidence demonstrating that variable aortic flow and wall shear stress conditions modulate vascular inflammation, this SCCOR proposes to: 1) Identify and validate novel biomarkers and imaging strategies for AAA disease stratification, 2) Test the ability of exercise therapy to suppress small AAAs, and 3) Investigate key molecular and cellular events present during experimental AAA evolution to identify and refine novel therapeutic strategies. Project I (Thrombin-Cleaved Osteopontin in AAA) will examine the role of thrombin-cleaved osteopontin and its regulation in AAA, and determine if measurements of specific cleaved forms of osteopontin will serve as useful biomarkers for predicting disease progression. Project II (Signature Protein Profile to Identify AAAs) will develop a custom antibody-based protein array to test whether distinct signature protein profiles can be identified that will correlate with AAA of different sizes, and whether changes in these profiles can predict disease progression and response to intervention. Project III (Hemodynamics in AAA Progression) will characterize the hemodynamics in the infrarenal aorta of patients with AAA, under both resting and exercise conditions, using MRI-based imaging techniques. We will examine how the shape, size, or vessel wall structure of the aortic aneurysm influence the hemodynamic parameters in AAA and test whether these changes in flow and vessel wall characteristics predict disease progression and response to intervention. Project IV (Evaluation of Exercise Therapy in Small AAA) is the key project in this SCCOR application. A prospective randomized trial will be carried out to test whether a supervised and sustained exercise program will reduce the rate of expansion of small AAA in patients. This clinical trial will anchor and connect all the other projects of this SCCOR. The proposed SCCOR will enable many accomplished investigators with complementary expertise to develop a coordinated and integrated approach to analysis, stratification and treatment of AAA disease, and fulfills the SCCOR objective of translating knowledge into clinical practice.

描述（由申请人提供）： 腹部主动脉瘤（AAA）是老年美国人的常见，病态且经常致命的疾病。 AAA疾病中的主要临床挑战包括：1）有效的非手术疗法预防早期疾病的进展，以及2）经过验证的生物标志物或有效的成像指数来监测疾病活动并指导小动脉瘤中的抑制性医疗疗法。 Based on extensive prior evidence demonstrating that variable aortic flow and wall shear stress conditions modulate vascular inflammation, this SCCOR proposes to: 1) Identify and validate novel biomarkers and imaging strategies for AAA disease stratification, 2) Test the ability of exercise therapy to suppress small AAAs, and 3) Investigate key molecular and cellular events present during experimental AAA evolution to identify and refine novel therapeutic strategies.项目I（AAA中的凝血酶裂解的骨桥蛋白）将检查凝血酶裂解的骨桥蛋白的作用及其在AAA中的调节，并确定是否测量了特定切割形式的骨桥蛋白的测量值是否将作为预测疾病进展的有用的生物标志物。项目II（识别AAAS的特征蛋白谱）将开发基于自定义的抗体蛋白阵列，以测试是否可以鉴定出与不同大小的AAA相关的不同特征蛋白谱，以及这些特征的变化是否可以预测疾病进展和对干预的反应。项目III（AAA进展中的血液动力学）将使用基于MRI的成像技术在静止和运动条件下的静脉和运动条件下的室外患者的血液动力学表征。我们将研究主动脉瘤的形状，大小或血管壁结构如何影响AAA中的血液动力学参数，并测试这些流量和血管壁特征的这些变化是否可以预测疾病的进展和对干预的反应。项目IV（小型AAA中的运动疗法评估）是此SCCOR应用程序的关键项目。将进行一项前瞻性随机试验，以测试受监督和持续的运动计划是否会降低患者小型AAA的扩张率。该临床试验将锚定并连接该SCCOR的所有其他项目。拟议的SCCOR将使许多具有互补专业知识的研究人员能够开发一种协调和综合的方法来分析，分层和治疗AAA疾病，并实现将知识转化为临床实践的SCCOR目标。