Imbalance in thioredoxin system activates NLRP3 inflammasome pathway in epicardial adipose tissue of patients with coronary artery disease

Atherosclerosis is the leading cause of death worldwide and has in part an inflammatory basis. Since epicardial adipose tissue (EAT) is in close contact with coronary arteries we hypothesized that an imbalance in thioredoxin-1 (TRX-1) and thioredoxin interacting protein (TXNIP) in EAT, activates NLRP3 inflammasome and promotes production of IL-1 beta, leading to the development of atherosclerosis. Thirty-eight patients with coronary artery disease (CAD) and thirty patients with no clinical signs of atherosclerosis who underwent open-heart surgery for valve replacement were classified as CAD and control groups, respectively. Biopsy samples from EAT were collected and expression of TXNIP, TRX-1, NLRP3 and IL-1 beta genes were assessed using qRT-PCR. Tissue protein levels of TXNIP and TRX-1 were determined by Western blotting while ELISA was applied to measure IL-1 beta. Haematoxylin and eosin staining was used for histological examination. mRNA and protein levels of TXNIP in EAT were significantly higher in patients with CAD compared with control group, whereas CAD patients showed lower TRX-1 gene and protein expression. In addition, in CAD patients the NLRP3 gene expression was almost doubled and IL-1 beta significantly increased at the both mRNA and protein levels. Enhancment in NLRP3 gene expression and TXNIP protein levels were accompanied with the increase in IL-1 beta protein level whereas TRX-1 protein content showed a negative correlation with IL-1 beta level. Concurrent increase in TXNIP, NLRP3, and IL-1 beta suggests possible involvement of thioredoxin system in the activation of NLRP3 inflammasome, production of IL-1 beta, and the presence of inflammation in CAD patients.

Automated summary

The study found significantly higher levels of TXNIP and NLRP3, and decreased levels of TRX-1 in EAT of patients with CAD, leading to a significant increase in IL-1 beta. These results suggest the possible involvement of the thioredoxin system in regulating inflammation in CAD patients.