TXNIP activates NLRP3/IL-1β and participate in inflammatory response and oxidative stress to promote deep venous thrombosis

• Published in: Experimental biology and medicine (Maywood, N.J.) Vol. 248; no. 18; pp. 1588 - 1597
• Main Authors: Fei, Jianwen, Wang, Haixia, Han, Jin, Zhang, Xuefeng, Ma, Hongfu, Qin, Xiao, Yu, Chaoxiao, Jiang, Junjie
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.09.2023
• Subjects: Animals; Cell Cycle Proteins - metabolism; Inflammasomes - metabolism; Interleukin-1beta - metabolism; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLR Proteins - metabolism; Original Research; Oxidative Stress; Rats; Rats, Sprague-Dawley; Thioredoxins - metabolism; Thrombosis; Venous Thrombosis; pathological change; Inflammation; MCC950; thioredoxin; oxidative stress; venous thrombosis
• ISSN: 1535-3702; 1535-3699
• DOI: 10.1177/15353702231191124

Increasing evidence indicates that deep venous thrombosis (DVT) is a common peripheral vascular disease. This study aims to investigate the mechanisms of thioredoxin-interacting protein (TXNIP) and nod-like receptor protein 3 (NLRP3) inflammasome in deep venous thrombosis (DVT). A total of 66 Sprague–Dawley (SD) rats were employed to conduct DVT model. DVT rat was treated with silenced TXNIP (si-TXNIP) lentivirus and MCC950 (a NLRP3 inhibitor). The thrombosis weight and weight/length ratio, tissue factor, inflammatory factors, superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) were measured. Hematoxylin–eosin (H&E) staining was used to investigate the pathological change. Western blotting was used to determine the protein expression level. The expression level of thioredoxin (TRx) was suppressed, whereas TXNIP and NLRP3 were elevated in DVT rat. Si-TXNIP or MCC950 could reduce the thrombosis weight and weight/length ratio, ameliorate the pathological change, and decrease inflammatory reaction. Mechanistically, si-TXNIP or MCC950 inhibited the expression levels of TXNIP, NLRP3, and interleukin (IL)-1β while elevating the TRx level, thereby suppressing the DVT. Our study indicated that si-TXNIP or MCC950 injection rescued the injury of vein induced by DVT. The possible mechanisms connected with the inhibition of TXNIP and NLRP3. TXNIP is a possible therapeutic target for DVT.