Abstract 17779: Osteoprotegerin and Abdominal Aortic Aneurysm Disease
Introduction: Osteoprotegerin (OPG) levels in blood have previously been associated with abdominal aortic aneurysm (AAA) growth. In vitro experiments demonstrated a stimulating effect of OPG on matrix metalloprotease 2 and 9 (MMP) activity in monocytes and vascular smooth muscle cells (VSMC). In the current study, we investigated OPG at tissue level in AAA disease. We assessed the hypothesis that OPG is locally present and produced in vessel walls of AAA disease and influences proteolysis in the AAA vessel wall.
Methods: Ventral AAA tissue was collected from 200 patients at the site of maximal diameter during open repair and was divided in two segments, one part for biochemical measurements and one part for histological analyses. We measured OPG, total cathepsin A, B, S levels, MMP-2 and MMP-9 activities. Histological segments were analyzed semi-quantitatively for presence of collagen, elastin, VSMC, macrophages, lymphocytes, plasma cells and stained for OPG.
Results: We observed a positive correlation of OPG with aortic diameter (< 5.5cm 3828±4836 pg/ml; 5.5–7cm 4262±5202 pg/ml; >7.0cm 4672±9092 pg/ml; p = 0.037). OPG correlated positively with MMP-2 and MMP-9 activity (r=0.185, p=0.010; r=0.168, p=0.020). However, stronger biochemical correlations were observed with cathepsin A, B and S (r=0.37, p<0.001; r=0.45, p<0.001; r=0.57, p<0.001). Immunohistochemistry showed that OPG staining was present in VSMC and plasma cell cytoplasm. VSMC in the medial aortic layer (semi-quantitatively analyzed as: no vs. minor vs. moderate vs. heavy staining) were significantly associated with OPG levels (no staining 4177±4771 pg/ml; minor 4508±6322 pg/ml; moderate 6559±13421 pg/ml; heavy 5696±6230 pg/ml, respectively; p = 0.04). Adventitial plasma cells were also significantly associated with OPG levels (no staining 3130±4434 pg/ml; minor 4250±8370 pg/ml; moderate 5901±4920 pg/ml; heavy 9480±16060 pg/ml, respectively; p < 0.001).
Conclusions: OPG is present in AAA vessel walls and expressed in medial VSMC and adventitial plasma cells. Locally measured OPG is associated with measures of proteolysis in the AAA vessel wall and with AAA diameter, suggesting a role for OPG in AAA progression and pathogenesis.
- © 2010 by American Heart Association, Inc.