Reduced endothelial thioredoxin‐interacting protein protects arteries from damage induced by metabolic stressin vivo

Abstract

Although thioredoxin-interacting protein (TXNIP) is involved in a variety of biologic functions, the contribution of endothelial TXNIP has not been well defined. To investigate the endothelial function of TXNIP, we generated a TXNIP knockout mouse on the Cdh5-cre background (TXNIP cdh5). Control (TXNIP) and TXNIP cdh5 mice were fed a high protein-low carbohydrate (HP-LC) diet for 3 mo to induce metabolic stress. We found that TXNIP and TXNIP cdh5 mice on an HP-LC diet displayed impaired glucose tolerance and dyslipidemia concretizing the metabolic stress induced. We evaluated the impact of this metabolic stress on mice with reduced endothelial TXNIP expression with regard to arterial structure and function. TXNIP cdh5 mice on an HP-LC diet exhibited less endothelial dysfunction than littermate mice on an HP-LC diet. These mice were protected from decreased aortic medial cell content, impaired aortic distensibility, and increased plasminogen activator inhibitor 1 secretion. This protective effect came with lower oxidative stress and lower inflammation, with a reduced NLRP3 inflammasome expression, leading to a decrease in cleaved IL-1β. We also show the major role of TXNIP in inflammation with a knockdown model, using a TXNIP-specific, small interfering RNA included in a lipoplex. These findings demonstrate a key role for endothelial TXNIP in arterial impairments induced by metabolic stress, making endothelial TXNIP a potential therapeutic target.-Bedarida, T., Domingues, A., Baron, S., Ferreira, C., Vibert, F., Cottart, C.-H., Paul, J.-L., Escriou, V., Bigey, P., Gaussem, P., Leguillier, T., Nivet-Antoine, V. Reduced endothelial thioredoxin-interacting protein protects arteries from damage induced by metabolic stress in vivo.

Aspirin alleviates endothelial gap junction dysfunction through inhibition of NLRP3 inflammasome activation in LPS-induced vascular injury

“…The present study demonstrates that inflammasomes participate in endothelial dysfunction30., 31., and ECD is the bedrock of diverse cardiovascular, renal, and metabolic diseases. Therefore, we believe the prevention and treatment of endothelial cell is the best choice to treatment cardiovascular diseases at the early stage.…”

Liposomes as Gene Delivery Vectors for Human Placental Cells

“…Indeed, nucleic acid internalization is only a part of the complex gene delivery process and does not necessarily imply knock-down of the gene of interest. A potential correlation between cellular internalization and transfection efficiency is however probable with the tested formulations as in vivo gene silencing was demonstrated for two of them in previous investigations [ 10 , 12 , 17 ].…”

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Stressing out the mitochondria: Mechanistic insights into NLRP3 inflammasome activation

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