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

Abstract

Objectives

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.

HIGHLIGHTS

Si-circABCA1 inhibits VMSC malignant proliferation, inflammation, and phenotypic switch.

miR-885–5p blocks the promoting effects of circABCA1 on VMSCs.

CircABCA1 regulates the miR-885–5p/ROCK2 axis in VMSCs.

Knockdown of circABCA1 reduces arterial plaque size and improves inflammation in AS mice.