An abdominal aortic aneurysm (AAA) is defined as a pathologic dilatation of the infrarenal aorta that isoften accompanied by significant superimposed atherosclerosis, inflammation and thrombosis. While AAAs arecommon 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 ofinflammation, apoptosis, extracellular matrix breakdown and thrombosis. Thus, by interrogation of serum withcustom protein microarrays, we anticipate that we will identify unique patterns of vascular-derived proteins thatwill serve as sensitive and specific markers of AAA development. In addition, protein profiles can be monitoredfor prediction of aneurysm expansion as well as response to therapy. Therefore, we propose to address thefollowing specific aims:
SPECIFIC AIM 1 : To develop an antibody-based planar array providing simultaneous abundancemeasurements 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 toidentify protein patterns that correlate with AAA formation.
SPECIFIC AIM 3 : To conduct a longitudinal prospective study in cases to identify predictors of aneurvsmprogression.
SPECIFIC AIM 4 : To determine protein profiles in patients undergoing active intervention for AAA anddetermine if beneficial response to therapy can be ascertained.
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