Expression of NAD(P)H:Quinone Oxidoreductase 1 and Its Significance in Human Abdominal Aortic Aneurysmal Tissues

Abstract

Background NAD(P)H:quinone oxidoreductase 1 (NQO1) protein protects cells against redox cycling of quinones and oxidative stress. Oxidative stress represents key mechanisms leading to abdominal aortic aneurysm (AAA) formation. However, a role of NQO1 in AAA formation has not been investigated previously.Methods The Tandem Mass Tag (TMT) labeling quantitative proteomics technique was utilized to detect 3 AAA tissues and 3 corresponding adjacent normal abdominal aorta tissue specimens. Immunohistochemistry was used to detect NQO1 expression in 8 AAA tissues, and the correlation with AAA size, MDA and SOD levels was analyzed. The senescence model of human vascular smooth muscle cell (VSMCs) induced by Angiotensin II (AngII) was established in vitro. The effect of AngII on the level of reactive oxygen species (ROS) and β-galactosidase activity of VSMCs were observed after NQO1 expression was inhibited by specific interfering RNA (si-NQO1) technique.Results NQO1 expression was the highest up-regulation (3.1fold) among 11 differentially expressed oxidative stress-related proteins (> 1.2 or<0.83 and P<0.05), and the expression of NQO1 was positively correlated with the AAA size (R2=0.517, P<0.05) and MDA level (R2=0.659, P<0.05). AngII treatment of human VSMCs increased ROS expression and β-galactosidase activity, while knocking down NQO1 expression promoted AngII-induced ROS production and cell aging. Conclusion Up-regulation of NQO1expression plays an antioxidant role in AAA, and it is expected to be a biomarker for early diagnosis and prognosis assessment of AAA.