Compared with control mice, increased plasma lipids and proinflammatory interleukin-1β, aggravated macrophage infiltration into the atherosclerotic lesion, and accelerated development of atherosclerosis were observed in diabetic mice, which were associated with the activation of NLRP3 inflammasomes and dysregulation of thioredoxin-1 and thioredoxin-interacting protein.
Interestingly, Nrf2 and Trx-1 can act together as well as independently of each other in protection against atherosclerosis and ischemia and reperfusion injury.
These results suggest that Trx1 inherently suppresses VCAM-1 and ICAM-1 expression in vascular endothelia and may prevent the initiation of atherosclerosis by attenuating adhesion molecule expression.
Thioredoxin and binding proteins (ASK1 and TBP2) appear to control apoptosis or metabolic states such as carbohydrate and lipid metabolism related to diseases such as diabetes and atherosclerosis.
Chemical modification of Trx1 by common environmental and endogenously generated reactive aldehydes can contribute to atherosclerosis development by interfering with antioxidant and redox signaling functions of Trx1.
We conclude that macrophage uptake of oxidized LDL induces a coordinated up-regulation of genes of the glutathione and thioredoxin systems, suggesting that these systems may participate in the cellular defense against oxidized LDL and possibly modulate the development of atherosclerosis.