Circ_0104652 Promotes the Proliferation and Migration of ox-LDL-Stimulated Vascular Smooth Muscle Cells via Stabilizing ADAMTS7 and HMGB1

• Published in: American journal of hypertension 2024-06, Vol.37 (7), p.465-476
• Main Authors: Bian, Bo, Chen, Heye, Teng, Tianming, Huang, Jinyong, Yu, Xuefang
• Format: Article
• Language: English
• Subjects: ADAMTS7 Protein - genetics; ADAMTS7 Protein - metabolism; Apoptosis - drug effects; Atherosclerosis - genetics; Atherosclerosis - metabolism; Atherosclerosis - pathology; Cell Movement - drug effects; Cell Proliferation - drug effects; Cells, Cultured; HMGB1 Protein - genetics; HMGB1 Protein - metabolism; Humans; Lipoproteins, LDL - metabolism; Lipoproteins, LDL - pharmacology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - pathology; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - pathology; RNA, Circular - genetics; RNA, Circular - metabolism; Signal Transduction
• ISSN: 0895-7061; 1941-7225; 1941-7225
• DOI: 10.1093/ajh/hpae026

Abstract BACKGROUND Atherosclerosis (AS) stands as the primary contributor to cardiovascular disease, a pervasive global health concern. Extensive research has underscored the pivotal role of circular RNAs (circRNAs) in cardiovascular disease development. However, the specific functions of numerous circRNAs in AS remain poorly understood. METHODS Quantitative real-time PCR analysis revealed a significant upregulation of circ_0104652 in oxidized low-density lipoprotein (ox-LDL)-induced vascular smooth muscle cells (VSMCs). Loss-of-function experiments were subsequently employed to assess the impact of circ_0104652 on ox-LDL-induced VSMCs. RESULTS Silencing circ_0104652 was found to impede the proliferation and migration while promoting the apoptosis of ox-LDL-stimulated VSMCs. Mechanistic assays unveiled that circ_0104652 stabilized ADAM metallopeptidase with thrombospondin type 1 motif 7 (ADAMTS7) and high mobility group box 1 (HMGB1) by recruiting eukaryotic translation initiation factor 4A3 (EIF4A3) protein. Rescue assays further confirmed that circ_0104652 exerted its influence on ox-LDL-induced VSMC proliferation through modulation of ADAMTS7 and HMGB1. CONCLUSIONS This study elucidates the role of the circ_0104652/EIF4A3/ADAMTS7/HMGB1 axis in ox-LDL-stimulated VSMCs, providing valuable insights into the intricate mechanisms involved. Graphical Abstract Graphical Abstract