Exploring Thioredoxin‐Interacting Protein (TXNIP) as a Therapeutic Target for Cardiovascular Diseases

Cardiovascular diseases (CVDs) are the primary causes of death globally. Risk factors such as aging, poor lifestyle, and genetics significantly influence how these diseases progress, with oxidative stress being an important factor in their pathogenesis. Thioredoxin-interacting protein (TXNIP), a redox regulator, has emerged as a crucial mediator in oxidative stress-mediated CVD. TXNIP is a pro-oxidant that disrupts thioredoxin (TRX) antioxidant function and produces a redox imbalance that triggers vascular damage, endothelial dysfunction, and CVD progression. TXNIP has been shown to trigger the release of the proinflammatory cytokines IL-1β and IL-18, by activating inflammatory signaling through the NLRP3 inflammasome. By altering the interaction between TRX and ASK1, TXNIP regulates apoptosis and pyroptosis, which triggers cell death following oxidative stress. The present review highlights TXNIP's role in the progression of CVD by regulating various signaling pathways such as TXNIP/SIRT1/FOXO1, TXNIP/Redd1, TLR4/NF-κB/TXNIP/NLRP3, and NRF2/TXNIP. The review further explores TXNIP's potential as a therapeutic target in CVD intervention.