Research Paper Volume 11, Issue 17 pp 7021—7035

Reduced NRF2 expression suppresses endothelial progenitor cell function and induces senescence during aging

Ruiyun Wang1, , Lihua Liu1, , Hongxia Liu1, , Kefei Wu1, , Yun Liu1, , Lijuan Bai1, , Qian Wang1, , Benming Qi2, , Benling Qi1, , Lei Zhang3, ,

  • 1 Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
  • 2 Department of Otorhinolaryngology, First People’s Hospital of Yunnan Province, Kunming, Yunnan 650000, China
  • 3 Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

Received: October 15, 2018       Accepted: August 21, 2019       Published: September 8, 2019
How to Cite

Copyright © 2019 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Aging is associated with an increased risk of cardiovascular disease. Numerical and functional declines in endothelial progenitor cells (EPCs) limit their capacity for endothelial repair and promote the development of cardiovascular disease. We explored the effects of nuclear factor (erythroid-derived 2)-like 2 (NRF2) on EPC activity during aging. Both in vitro and in vivo, the biological functioning of EPCs decreased with aging. The expression of NRF2 and its target genes (Ho-1, Nqo-1 and Trx) also declined with aging, while Nod-like receptor protein 3 (NLRP3) expression increased. Aging was associated with oxidative stress, as evidenced by increased reactive oxygen species and malondialdehyde levels and reduced superoxide dismutase activity. Nrf2 silencing impaired the functioning of EPCs and induced oxidative stress in EPCs from young mice. On the other hand, NRF2 activation in EPCs from aged mice protected these cells against oxidative stress, ameliorated their biological dysfunction and downregulated the NLRP3 inflammasome. These findings suggest NRF2 can prevent the functional damage of EPCs and downregulate the NLRP3 inflammasome through NF-κB signaling.


CVD: cardiovascular disease; NLRP3: Nod-like receptor protein 3; Dil-acLDL: 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindo-carbocyanine-labeled acetylated low density lipoprotein; EPCs: endothelial progenitor cells; HO-1: Heme oxygenase-1; KEAP1: Kelch-like ECH-associated protein-1; NO: nitric oxide; NQO-1: Quinone oxidoreductase-1; NRF2: Nuclear factor (erythroid-derived 2)-like 2; PBS: phosphate-buffered saline; ROS: reactive oxygen species; SOD: Superoxide dismutase; tBHQ: tert-butylhydroquinone; VEGF: Vascular endothelial growth factor; VEGFR2: Vascular endothelial growth factor receptor 2.