Signature Protein Profiles to Identify AAAs

Stanford University, Stanford CA

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Abstract

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