Increased levels of thioredoxin in patients with abdominal aortic aneurysms (AAAs). A potential link of oxidative stress with AAA evolution

Abstract

Objective: Oxidative stress is a main mechanism involved in vascular pathologies. Increased thioredoxin (TRX) levels have been observed in several oxidative stress-associated cardiovascular diseases. We aim to test the potential role of TRX as a biomarker of oxidative stress in abdominal aortic aneurysm (AAA).

Methods: TRX levels were analysed in both AAA intraluminal thrombus (ILT) tissue and in tissue-conditioned media by immunohistochemistry, Western blot and ELISA. Moreover, serum TRX levels were assessed in AAA Caucasian patients by ELISA.

Results: TRX was mainly localized in the luminal part of ILT in AAA. Compared with the abluminal layer, TRX release was increased in the luminal layer of the ILT of AAA (31+/-9 ng/ml vs. 9+/-3 ng/ml, p<0.05). The interest of this approach is that we can identify proteins potentially released into the blood compartment, which could serve as biomarkers of the pathology. In a training population, serum TRX levels were significantly increased in patients with AAA relative to healthy subjects (50+/-6 ng/ml vs. 26+/-3 ng/ml, p<0.05). These results were validated in a second independent group of patients. Moreover, a positive correlation between TRX and AAA size (rho=0.5, p<0.001) was observed. Finally, in AAA samples with follow-up, TRX was positively associated to aneurismal growth rate (rho=0.25, p=0.027).

Conclusions: TRX release is increased in the luminal part of AAA and TRX serum levels are increased in AAA patients compared with healthy subjects. TRX levels correlates with AAA size and expansion, suggesting its potential role as a biomarker of AAA evolution.