Downregulation of LncRNA NORAD Promotes Ox-LDL-induced Vascular Endothelial Cell Injury and Atherosclerosis

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2020 Apr 9

PMID 32267831

Citations 68

Authors

Weihua Bian

Xiaohong Jing

Zhiyu Yang

Zhen Shi

Ruiyao Chen

Aili Xu

Na Wang

Jing Jiang

Cheng Yang

Daolai Zhang

Lan Li

Haiyan Wang

Juan Wang

Yeying Sun

Chunxiang Zhang

Affiliations

Soon will be listed here.

Abstract

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 and 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.

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