LncRNA PSMB8-AS1 Instigates Vascular Inflammation to Aggravate Atherosclerosis

作者：Shu Li, Run-Chao He, S Wu, Yu Song, Kelan Zhang, Mao-Lin Tang, Yanrou Bei, Ting Zhang, Jin-Bo Lu, Xin Ma, Min Jiang, Liang-Jun Qin, Yudan Xu, Xian-Hui Dong, Jia Wu, Xiaoyan Dai, Yan‐Wei Hu · 发表于：Circulation Research · 年份：2023 · DOI：10.1161/circresaha.122.322360 · 被引用次数：71 · 研究领域：Cancer-related molecular mechanisms research、Lipid metabolism and disorders、Atherosclerosis and Cardiovascular Diseases

BACKGROUND: Increasing evidence suggests that long noncoding RNAs play significant roles in vascular biology and disease development. One such long noncoding RNA, PSMB8-AS1 , has been implicated in the development of tumors. Nevertheless, the precise role of PSMB8-AS1 in cardiovascular diseases, particularly atherosclerosis, has not been thoroughly elucidated. Thus, the primary aim of this investigation is to assess the influence of PSMB8-AS1 on vascular inflammation and the initiation of atherosclerosis. METHODS: We generated PSMB8-AS1 knockin and Apoe (Apolipoprotein E) knockout mice ( Apoe −/− PSMB8-AS1 KI ) and global Apoe and proteasome subunit-β type-9 ( Psmb9 ) double knockout mice ( Apoe −/− Psmb9 −/− ). To explore the roles of PSMB8-AS1 and Psmb9 in atherosclerosis, we fed the mice with a Western diet for 12 weeks. RESULTS: Long noncoding RNA PSMB8-AS1 is significantly elevated in human atherosclerotic plaques. Strikingly, Apoe −/− PSMB8-AS1 KI mice exhibited increased atherosclerosis development, plaque vulnerability, and vascular inflammation compared with Apoe −/− mice. Moreover, the levels of VCAM1 (vascular adhesion molecule 1) and ICAM1 (intracellular adhesion molecule 1) were significantly upregulated in atherosclerotic lesions and serum of Apoe −/− PSMB8-AS1 KI mice. Consistently, in vitro gain- and loss-of-function studies demonstrated that PSMB8-AS1 induced monocyte/macrophage adhesion to endothelial cells and increased VCAM1 and ICAM1 levels in a PSMB9-dep...