CircARCN1 aggravates atherosclerosis by regulating HuR-mediated USP31 mRNA in macrophages

作者：Zhicheng Pan, Jialan Lv, Liding Zhao, Kaidi Xing, Run‐Ze Ye, Yuesheng Zhang, Siyuan Chen, Peng Yang, Hailong Yu, Yangkai Lin, Ruobing Li, Dongfei Wang, Juan Fang, Dong Yang, Jianpeng Sheng, Xiaolin Wang, Ge Shan, Shan Zhang, Hongqiang Cheng, Qingbo Xu, Xiaogang Guo · 发表于：Cardiovascular Research · 年份：2024 · DOI：10.1093/cvr/cvae148 · 被引用次数：16 · 研究领域：Circular RNAs in diseases、Nuclear Structure and Function、Cardiovascular Disease and Adiposity

AIMS: Circular RNAs (circRNAs) are considered important regulators of biological processes, but their impact on atherosclerosis development, a key factor in coronary artery disease (CAD), has not been fully elucidated. We aimed to investigate their potential use in patients with CAD and the pathogenesis of atherosclerosis. METHODS AND RESULTS: Patients with stable angina (SA) or acute coronary syndrome (ACS) and controls were selected for transcriptomic screening and quantification of circRNAs in blood cells. We stained carotid plaque samples for circRNAs and performed gain- and loss-of-function studies in vitro. Western blots, protein interaction analysis, and molecular approaches were used to perform the mechanistic study. ApoE-/- mouse models were employed in functional studies with adeno-associated virus-mediated genetic intervention. We demonstrated elevated circARCN1 expression in peripheral blood mononuclear cells from patients with SA or ACS, especially in those with ACS. Furthermore, higher circARCN1 levels were associated with a higher risk of developing SA and ACS. We also observed elevated expression of circARCN1 in carotid artery plaques. Further analysis indicated that circARCN1 was mainly expressed in monocytes and macrophages, which was also confirmed in atherosclerotic plaques. Our in vitro studies provided evidence that circARCN1 affected the interaction between HuR and ubiquitin-specific peptidase 31 (USP31) mRNA, resulting in attenuated USP31-mediated NF-κ...