环状 RNA-ABCA1 促进氧化型低密度脂蛋白诱导的血管平滑肌细胞炎症反应和表型转化。

Circ-ABCA1 promotes oxidized low-density lipoprotein-induced inflammation and phenotypic switch in vascular smooth muscle cells.

机构信息

Department of Cardiac Catheterization Room, Yantaishan Hospital, Yantai City, Shandong Province, China.

Department of Emergency, Ezhou Central Hospital, Ezhou City, Hubei Province, China.

出版信息

Clinics (Sao Paulo). 2024 Mar 28;79:100343. doi: 10.1016/j.clinsp.2024.100343. eCollection 2024.

DOI:10.1016/j.clinsp.2024.100343

PMID:38554490

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10998038/

Abstract

OBJECTIVE

Atherosclerosis (AS) is a chronic inflammatory disease of the arterial wall, in which Human Vascular Smooth Muscle Cells (HVSMCs) are involved. Nevertheless, the functions and mechanisms of circRNAs in oxidized Low-Density Lipoprotein (ox-LDL)-induced vascular smooth muscle cells remain unclear.

METHODS

Circ-ABCA1 expression was measured in the models of AS. Then, in the vitro model, oligonucleotide transfection was performed, followed by an analysis of VSMC proliferation, migration, inflammation, and phenotypic switch. Also, in the in vivo model, mice were injected with shRNA lentivirus, followed by histological examination of aortic tissues. Finally, the interaction of circ-ABCA1, miR-885-5p, and ROCK2 was identified.

RESULTS

Circ-ABCA1, was confirmed to be overexpressed in ox-LDL-induced VSMCs and mouse models of AS. Functionally, silencing circ-ABCA1 via oligonucleotide transfection suppressed VSMC proliferation, migration, inflammation, and phenotypic switch in vitro and prevented AS development in mice in vivo. Mechanistically, circ-ABCA1 absorbed miR-885-5p, which targeted ROCK2.

CONCLUSION

Taken together, the data from this study suggest that circ-ABCA1 mediates cellular inflammation and phenotype switching through the miR-885-5p/ROCK2 axis in ox-LDL-induced VSMCs, and the circ-ABCA1/miR-885-5p/ROCK2 axis is a new potential biomarker for the treatment of AS.

摘要

目的

动脉粥样硬化（AS）是动脉壁的一种慢性炎症性疾病，其中涉及人血管平滑肌细胞（HVSMCs）。然而，circRNAs 在氧化型低密度脂蛋白（ox-LDL）诱导的血管平滑肌细胞中的功能和机制仍不清楚。

方法

在 AS 模型中测量 circ-ABCA1 的表达。然后，在体外模型中进行寡核苷酸转染，随后分析 VSMC 增殖、迁移、炎症和表型转换。此外，在体内模型中，用 shRNA 慢病毒注射小鼠，然后对主动脉组织进行组织学检查。最后，鉴定 circ-ABCA1、miR-885-5p 和 ROCK2 的相互作用。

结果

circ-ABCA1 在 ox-LDL 诱导的 VSMC 和 AS 小鼠模型中被证实过表达。功能上，通过寡核苷酸转染沉默 circ-ABCA1 可抑制体外 VSMC 增殖、迁移、炎症和表型转换，并可预防体内 AS 的发展。机制上，circ-ABCA1 吸收靶向 ROCK2 的 miR-885-5p。