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

IF 3.2 3区医学 Q2 PERIPHERAL VASCULAR DISEASE

American Journal of Hypertension Pub Date : 2024-06-14 DOI:10.1093/ajh/hpae026

Bo Bian, Heye Chen, Tianming Teng, Jinyong Huang, Xuefang Yu

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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.

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Circ_0104652 通过稳定 ADAMTS7 和 HMGB1 促进氧化-LDL 刺激的血管平滑肌细胞的增殖和迁移。

背景：动脉粥样硬化（AS）是心血管疾病（CVD）的主要诱因，也是全球普遍关注的健康问题。大量研究强调了环状 RNA（circRNA）在心血管疾病发展中的关键作用。然而，人们对强直性脊柱炎中许多循环 RNA 的具体功能仍然知之甚少：方法：定量实时 PCR（RT-qPCR）分析显示，circ_0104652 在氧化低密度脂蛋白（ox-LDL）诱导的血管平滑肌细胞（VSMCs）中显著上调。随后采用功能缺失实验评估了 circ_0104652 对氧化低密度脂蛋白诱导的血管平滑肌细胞的影响：结果：研究发现，沉默 circ_0104652 会阻碍受 ox-LDL 刺激的血管内皮细胞的增殖和迁移，同时促进其凋亡。机理分析发现，circ_0104652通过招募真核翻译起始因子4A3（EIF4A3）蛋白，稳定了具有血栓软蛋白1型基序7（ADAMTS7）的ADAM金属肽酶和高迁移率组框1（HMGB1）。拯救实验进一步证实，circ_0104652通过调节ADAMTS7和HMGB1对ox-LDL诱导的VSMC增殖产生影响：本研究阐明了 circ_0104652/EIF4A3/ADAMTS7/HMGB1 轴在氧化-LDL 刺激的 VSMC 中的作用，为了解其中的复杂机制提供了宝贵的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

American Journal of Hypertension 医学-外周血管病

CiteScore

6.90

自引率

6.20%

发文量

144

审稿时长

3-8 weeks

期刊介绍： The American Journal of Hypertension is a monthly, peer-reviewed journal that provides a forum for scientific inquiry of the highest standards in the field of hypertension and related cardiovascular disease. The journal publishes high-quality original research and review articles on basic sciences, molecular biology, clinical and experimental hypertension, cardiology, epidemiology, pediatric hypertension, endocrinology, neurophysiology, and nephrology.