Research Paper Volume 12, Issue 7 pp 6385—6400

Downregulation of LncRNA NORAD promotes Ox-LDL-induced vascular endothelial cell injury and atherosclerosis

Weihua Bian1, *, , Xiaohong Jing1, *, , Zhiyu Yang2, , Zhen Shi3, , Ruiyao Chen4, , Aili Xu3, , Na Wang3, , Jing Jiang1, , Cheng Yang3, , Daolai Zhang1, , Lan Li1, , Haiyan Wang1, , Juan Wang1, , Yeying Sun1, , Chunxiang Zhang1,4, ,

  • 1 Department of Pharmacy, Binzhou Medical University, Yantai 264003, China
  • 2 Department of Gastroenterology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou 450003, China
  • 3 Department of Basic Medicine, Binzhou Medical University, Yantai 264003, China
  • 4 Children’s Heart Center, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou 325027, China
* Equal contribution

Received: October 27, 2019       Accepted: February 25, 2020       Published: April 8, 2020
How to Cite

Copyright © 2020 Bian 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.


Long noncoding RNAs (lncRNAs) play important roles in the development of vascular diseases. However, the effect of lncRNA NORAD on atherosclerosis remains unknown. This study aimed to investigate the effect NORAD on endothelial cell injury and atherosclerosis. Ox-LDL-treated human umbilical vein endothelial cells (HUVECs) and high-fat-diet (HFD)-fed ApoE−/− mice were used as in vitro and in vivo models. Results showed that NORAD-knockdown induced cell cycle arrest in G0/G1 phase, aggravated ox-LDL-induced cell viability reduction, cell apoptosis, and cell senescence along with the increased expression of Bax, P53, P21 and cleaved caspase-3 and the decreased expression of Bcl-2. The effect of NORAD on cell viability was further verified via NORAD-overexpression. NORAD- knockdown increased ox-LDL-induced reactive oxygen species, malondialdehyde, p-IKBα expression levels and NF-κB nuclear translocation. Proinflammatory molecules ICAM, VCAM, and IL-8 were also increased by NORAD- knockdown. Additionally, we identified the strong interaction of NORAD and IL-8 transcription repressor SFPQ in HUVECs. In ApoE−/− mice, NORAD-knockdown increased the lipid disorder and atherosclerotic lesions. The results have suggested that lncRNA NORAD attenuates endothelial cell senescence, endothelial cell apoptosis, and atherosclerosis via NF-κB and p53–p21 signaling pathways and IL-8, in which NORAD-mediated effect on IL-8 might through the direct interaction with SFPQ.


lncRNA: long noncoding RNA; ox-LDL: oxidized low-density lipoprotein; HUVECs: human umbilical vein endothelial cells; HFD: high-fat-diet; ApoE−/−: apolipoprotein E-deficient; LOX-1: low-density lipoprotein receptor 1; ROS: reactive oxygen species; SA-β-gal: senescence associated-beta-galactosidase; siNORAD: small interfering RNA-targeting NORAD; siCTRL: control small-interfering RNA; CCK-8: Cell Counting Kit-8; H&E: hematoxylin and eosin; MDA: malondialdehyde; RIP: RNA-binding protein immunoprecipitation.