Signature Protein Profiles to Identify AAAs

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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.