Abstract 223: Is Oxidative Stress Important in AAA pathogenesis?

OBJECTIVE Active investigations continue to identify markers other than size that would predict a risk of abdominal aortic aneurysms (AAA) rupture. Circulating biomarkers could also indicate optimal intervals between the surveillance intervals. Finally, the identification of biomarkers also may identify potential pathogenic pathways, and thus may open possibilities for pharmacological inhibition of growth. In the search of novel biomarkers of AAA progression, serum and wall material proteins were analyzed by a differential proteomic approach. METHODS AND RESULTS The same layers of AAA wall from ruptured (rAAA) and non-ruptured AAA were incubated, and the proteins released were analyzed by 2-dimensional difference in-gel electrophoresis. Proteins from serum were analyzed and correlated with AAA annual expansion rate. Several differentially expressed proteins involved in main AAA pathological mechanisms were identified by mass spectrometry. Among the 8 proteins identified in AAA wall, peroxiredoxin-2 (PRX-2) was more permanent, which was further validated by Western blot and immunohistochemistry. We demonstrated increased PRX-2 levels in rAAA patient wall material compared with AAA subjects and also positive correlation in serum among PRX-2 and AAA diameter and annual AAA expansion rate. CONCLUSIONS Eight proteins associated with AAA pathogenesis have been identified in AAA wall by a proteomic approach. Protein profiles identified in the wall from the rAAA and the serum would appear to be a convenient monitoring tool that has the ability to be both sensitive and specific for AAAs. Among them, PRX-2 serum levels are increased in AAA patients and correlate with AAA size and growth rate, suggesting the potential use of PRX-2 as a biomarker for AAA evolution. Characterizing such diagnostic protein profiles, combined with known risk factors as well as emerging genetic data, would contribute to the long-term objective of applying effective non-surgical therapies to the treatment of small AAA disease. Larger studies are required to confirm the potential and clinical role of the identified proteins.