Differential Gene and Protein Expression is Associated with Hypoxia in the Human Abdominal Aortic Aneurysm (AAA) Wall

Abstract

The goal of this work was to investigate the hypothesis that AAA wall exposed to hypoxia as a result of being adjacent to a thick intralumenal thrombus (ILT) exhibits impaired remodeling, leading to further degeneration. Pairs of AAA wall, selected based on disparate thicknesses of adjacent ILT, were snap frozen. QPCR was used to compare the gene expression. Protein levels were measured with Western blotting. MMP‐2 and ‐9 levels were measured with gelatin zymography. In separate paired samples, total wall thickness was measured on H&E‐stained sections. We found the activity, expression, and amounts of some genes and proteins to vary with ILT thickness within a given AAA, while others were at least spatially variable at the current sample number. For example, iNOS gene expression was up‐regulated in regions of AAA wall adjacent to thick ILT. Some protein levels were correlated to fold changes in ILT thickness. For example, calponin protein levels are negatively correlated to the fold increase in ILT thickness. AAA wall thickness was positively correlated to ILT thickness. The results support our hypothesis, suggesting that compared to AAA wall near thin ILT, the AAA wall adjacent to thick ILT has variable protein expression and impaired remodeling mechanisms. This work was supported by NIH R01‐HL79313.