标题：Protective role of NRF2 in macrovascular complications of diabetes
作者：Wu, Junduo; Sun, Xiaodan; Jiang, Ziping; Jiang, Jun; Xu, Linlin; Tian, Ao; Sun, Xuechun; Meng, Huali; Li, Ying; Huang, Wenlin; Jia 更多 作者机构：[Wu, Junduo] Second Hosp Jilin Univ, Dept Cardiol, Changchun, Peoples R China.; [Sun, Xiaodan] Shandong Univ, Hosp 2, Cheeloo Coll Med, Intens Care 更多
通讯作者地址：Wu, H (corresponding author), Shandong Univ, Cheeloo Coll Med, Sch Publ Hlth, Dept Nutr & Food Hyg, 44 Wenhua Xi Rd, Jinan 250012, Shandong, Peoples R 更多
来源：JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
关键词：complications; diabetes; macrovascular; NRF2; oxidative stress
摘要：Macrovascular complications develop in over a half of the diabetic individuals, resulting in high morbidity and mortality. This poses a severe threat to public health and a heavy burden to social economy. It is therefore important to develop effective approaches to prevent or slow down the pathogenesis and progression of macrovascular complications of diabetes (MCD). Oxidative stress is a major contributor to MCD. Nuclear factor (erythroid-derived 2)-like 2 (NRF2) governs cellular antioxidant defence system by activating the transcription of various antioxidant genes, combating diabetes-induced oxidative stress. Accumulating experimental evidence has demonstrated that NRF2 activation protects against MCD. Structural inhibition of Kelch-like ECH-associated protein 1 (KEAP1) is a canonical way to activate NRF2. More recently, novel approaches, such as activation of theNfe2l2gene transcription, decreasing KEAP1 protein level by microRNA-induced degradation ofKeap1mRNA, prevention of proteasomal degradation of NRF2 protein and modulation of other upstream regulators of NRF2, have emerged in prevention of MCD. This review provides a brief introduction of the pathophysiology of MCD and the role of oxidative stress in the pathogenesis of MCD. By reviewing previous work on the activation of NRF2 in MCD, we summarize strategies to activate NRF2, providing clues for future intervention of MCD. Controversies over NRF2 activation and future perspectives are also provided in this review.