Abstract 17943: T Lymphocyte Activation and Oxidative Stress in the Development of Human Abdominal Aortic Aneurysms
The pathogenesis of abdominal aortic aneurysm (AAA) formation is complex and not clearly understood. Both inflammation and oxidative stress have been implicated. It has been suggested that distinct areas of AAA differ in relation to these mechanisms with neck area (NA) showing predominant inflammatory infiltration while the maximally dilated area is considered to be particularly oxidative stress prone. In the present study we compared leukocyte infiltration and vascular superoxide production in the NA, MD and compared it to transitional area (TA).
Methods: Flow cytometry of single cell suspensions of AAA and lucigenin enhanced chemiluminescence (5uM) were used to study AAA samples obtained from 38 patients undergoing AAA surgical repair.
Results: Infiltration of leukocytes in aneurysms wall was dramatically increased as compared to control aorta (1426±353 vs 60±39 cell/mg tissue, p<0.001), but it tended to increase from NA, TA to the MD region (respectively: 962±175 vs 1378±396 vs 1472±294 cell/mg tissue; NS). Similarly, T cell content was higher in AAA wall as compared to control aorta (270.8±53.8 vs 6.7±2.2 cell/mg tissue, p<0.001). While T cell numbers were not dramatically different between NA, MDA and TA, we observed that infiltrating CD4+T cell are highly activated, CD69 and CD25 increased strongly on T cells from aneurysmal wall in comparison to peripheral blood (PB), (CD69+ 45±2% vs. 1.5±0.3% and CD25+ 18±5 vs 9±1%; p<0.05). Similar activation was observed in CD8+ cells (CD69+: 3±0.5% vs 43±3%). As oxidative stress has been implicated as a driving force of inflammation in AAA we studied superoxide anion in 3 respective areas of AAA. Interestingly it was highest in the neck area, as compared to either TA or MDA (113±23 vs 67±17 or 60±18 RLU/s/mg, p<0.05).
Conclusions: Infiltration of leukocytes and lymphocytes T is higher in AAA in comparison to noAAA aorta and was increased throughout all studied areas of AAA. T cells derived from AAA wall are strongly activated. Surprisingly, higher superoxide production associates with lower T cell and leukocyte content within the neck area, which could indicate that oxidative stress, could precede, rather than coincide with inflammation in AAA.
- © 2013 by American Heart Association, Inc.