| Title | ICAM-1-related noncoding RNA accelerates atherosclerosis by amplifying NF-?B signaling |
| Authors | Ding, Shuangjin Liu, Jiankun Han, XiaoRui Ding, Wanqiu Liu, Zhirui Zhu, Ying Zhan, Wenxing Wan, Yiqi Gai, Shujie Hou, Junjie Wang, Xiaoxia Wu, Yixia Wu, Andong Li, Chuan-Yun Zheng, Zhe Tian, Xiao-Li Cao, Huiqing |
| Affiliation | Nanchang Univ, Aging & Vasc Dis, Human Aging Res Inst, 999 Xuefu Rd, Nanchang 330031, Jiangxi, Peoples R China Nanchang Univ, Sch Life Sci, 999 Xuefu Rd, Nanchang 330031, Jiangxi, Peoples R China Jiangxi Key Lab Human Aging, 999 Xuefu Rd, Nanchang 330031, Jiangxi, Peoples R China Peking Univ, Coll Future Technol, Inst Mol Med, Beijing 100871, Peoples R China Chinese Acad Med Sci & Peking Union Med Coll, Fuwai Hosp, Natl Clin Res Ctr Cardiovasc Dis, Natl Ctr Cardiovasc Dis,State Key Lab Cardiovasc, Beijing, Peoples R China |
| Keywords | KAPPA-B TNF-ALPHA INFLAMMATION ACTIVATION ICAM-1 EXPRESSION DISEASE RISK |
| Issue Date | Sep-2022 |
| Publisher | JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY |
| Abstract | Long noncoding RNAs (lncRNAs) are critical regulators of inflammation with great potential as new therapeutic targets. However, the role of lncRNAs in early atherosclerosis remains poorly characterized. This study aimed to identify the key lncRNA players in activated endothelial cells (ECs). The lncRNAs in response to pro inflammatory factors in ECs were screened through RNA sequencing. ICAM-1-related non-coding RNA (ICR) was identified as the most potential candidate for early atherosclerosis. ICR is essential for intercellular adhesion molecule-1 (ICAM1) expression, EC adhesion and migration. In a high fat diet-induced atherosclerosis model in mice, ICR is upregulated in the development of atherosclerosis. After intravenous injection of adenovirus carrying shRNA for mouse ICR, the atherosclerotic plaque area was markedly reduced with the declined expression of ICR and ICAM1. Mechanistically, ICR stabilized the mRNA of ICAM1 in quiescent ECs; while under inflammatory stress, ICR upregulated ICAM1 in a nuclear factor kappa B (NF-kappa B) dependent manner. RNA-seq analysis showed pro-inflammatory targets of NF-kappa B were regulated by ICR. Furthermore, the chromatin immunoprecipitation assays showed that p65 binds to ICR promoter and facilitates its transcription. Interestingly, ICR, in turn, promotes p65 accumulation and activity, forming a positive feedback loop to amplify NF-kappa B signaling. Preventing the degradation of p65 using proteasome inhibitors rescued the expression of NF-kappa B targets suppressed by ICR. Taken together, ICR acts as an accelerator to amplify NF-kappa B signaling in activated ECs and suppressing ICR is a promising early intervention for atherosclerosis through ICR/p65 loop blockade. |
| URI | http://hdl.handle.net/20.500.11897/648243 |
| ISSN | 0022-2828 |
| DOI | 10.1016/j.yjmcc.2022.06.001 |
| Indexed | SCI(E) |
| Appears in Collections: | 分子医学研究所 |
