Abstract 17211: Decreased Levels of Endothelial Nitric Oxide Synthase Protein in Different Areas of Ascending Aortic Aneurysms in Conjunction with Bicuspid Aortic Valve Can Influence the Cytosolic Protein Levels of Pro-Apoptotic Htra2/omi
Background: Dysregulated expression of endothelial nitric oxide synthase (eNOS) is observed in aortic aneurysms associated with bicuspid aortic valve (BAV). We determined eNOS protein levels in various areas of ascending aortic aneurysms.
Methods: Aneurysmal specimens were collected from 14 patients with BAV and 5 with tricuspid aortic valve (TAV). Concentrations of eNOS protein were measured in the outer curve (convexity), opposite side (concavity), distal, and above the sinotubular junction (proximal) areas of the aneurysm. Cultured aortic cells were treated with L-NAME, a NO synthase inhibitor, and the amounts of 35 apoptosis-related proteins were determined.
Results: In BAV patients, differences in eNOS protein levels were observed between the concavity (93.14 ± 48.47) vs. convexity areas (59.67 ± 46.03% of calibrator; p = 0.04), concavity (93.14 ± 48.47) vs. proximal areas (43.00 ± 53.38% of calibrator; p = 0.02), and distal (61.2 ± 31.8) vs. proximal areas (43.00 ± 53.38% of calibrator; p = 0.03). In the proximal aorta, eNOS protein levels were significantly higher in TAV (105.79 ± 75.11% of calibrator) than in BAV patients (43.00 ± 53.38%; p = 0.04). Inhibition of NO synthesis in aneurysmal aortic cells by L-NAME led to a cytosolic increase of the mitochondrial serine protease protein HTRA2/Omi (before: 63.1 ± 3.8, after: 72.6 ± 4.2% of calibrator; p = 0.04).
Discussion: Dysregulation of NO led to an increase in proapoptotic HTRA2/Omi. Low eNOS expression in the BAV proximal aorta may confer susceptibility to aneurysm formation. These findings contribute to our understanding of the involvement of eNOS proteins in ascending aortic aneurysm.
- © 2012 by American Heart Association, Inc.