期刊
AGING-US
卷 12, 期 7, 页码 6385-6400出版社
IMPACT JOURNALS LLC
DOI: 10.18632/aging.103034
关键词
NORAD; cell senescence; cell apoptosis; ox-LDL; IL-8
资金
- National Natural Science Foundation of China [81670398, 91639102, 81801192]
- Taishan Scholars of Shandong Province
- Young Teacher Development Program of Shandong Province
- Higher Educational Science and Technology Program of Shandong Province [J18KA141]
- Key Research and Development Program of Shandong Province [2019GSF108149]
- Natural Science Foundation of Shandong Province [ZR2019MH074]
- Key Projects of Zhejiang Provincial Natural Science Foundation [LZ17H250001]
- Key Research Project of Yantai City [2018ZHGY071, 2018ZHGY089]
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 GO/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-IKB alpha expression levels and NF-kappa B 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-kappa B 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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