Role of thioredoxin-interacting protein in mediating endothelial dysfunction in hypertension  

作　　者：Ruiyu Wang Yongzheng Guo Lingjiao Li Minghao Luo Linqian Peng Dingyi Lv Zhe Cheng Qian Xue Liang Wang Jing Huang 

机构地区：[1]Department of Cardiology,The Second Affiliated Hospital of Chongqing Medical University,Chongqing 400010,PR China [2]Department of Cardiology,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,PR China [3]Institute of Life Science,Chongqing Medical University,Chongqing 400016,PR China

出　　处：《Genes & Diseases》2022年第3期753-765,共13页基因与疾病（英文）

基　　金：The work was supported by the National Natural Science Foundation of China(No.81370440);the National Science-Technology Support Projects of China(No.2015BAI01B00).

摘　　要：Excessive oxidative stress is a major causative factor of endothelial dysfunction in hypertension.As an endogenous pro-oxidant,thioredoxin-interacting protein(TXNIP)contributes to oxidative damage in various tissues.The present study aimed to investigate the role of TXNIP in mediating endothelial dysfunction in hypertension.In vivo,an experimental model of acquired hypertension was established with two-kidney,one-clip(2K1C)surgery.The expression of TXNIP in the vascular endothelial cells of multiple vessels was significantly increased in hypertensive rats compared with sham-operated rats.Resveratrol,a TXNIP inhibitor,suppressed vascular oxidative damage and increased the expression and activity of eNOS in the aorta of hypertensive rats.Notably,impaired endothelium-dependent vasodilation was effectively improved by TXNIP inhibition in hypertensive rats.In vitro,we observed that Ang II increased the expression of TXNIP in primary human aortic endothelial cells(HAECs)and that TXNIP knockdown by RNA interference alleviated cellular oxidative stress damage and mitigated the impaired eNOS activation and intracellular nitric oxide(NO)production observed in Ang Il-treated HAECs.However,inhibiting thioredoxin(TRX)with PX-12 completely blunted the protective effect of silencing TXNIP.In addition,TXNIP knockdown facilitated TRX expression and promoted TRX nuclear translocation to further activate AP1 and REF1.TRX overexpressi on exhibited favorable effects on eNOS/NO homeostasis in Ang 11-treated HAECs.Thus,TXNIP contributes to oxidative stress and endothelial dysfunction in hypertension,and these effects are dependent on the antioxidant capacity of TRX,suggesting that targeting TXNIP may be a novel strategy for antihypertensive therapy.

关 键 词：Endothelial dysfunction ENOS HYPERTENSION Oxidative stress Thioredoxininteracting protein 

分 类 号：R3[医药卫生—基础医学]