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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. (AS wall HVSMCs (HVSMCs involved Nevertheless LowDensity Low Density oxLDLinduced ox LDL induced unclear CircABCA1 CircABCA Circ ABCA1 ABCA Circ-ABCA Then model performed proliferation migration Also lentivirus tissues Finally circABCA1, circABCA1 circABCA circ ABCA1, miR885–5p, miR8855p miRp miR 885–5p, 885 5p p miR-885–5p ROCK identified CircABCA1, Functionally circ-ABCA Mechanistically together miR885–5p/ROCK2 miR8855pROCK2 miRpROCK 885–5p/ROCK2 miR-885–5p/ROCK circABCA1/miR885–5p/ROCK2 circABCA1miR8855pROCK2 circABCAmiRpROCK ABCA1/miR circ-ABCA1/miR-885–5p/ROCK miR885 miR885–5p 8855p 885–5p 88 miR885–5p/ROCK pROCK miR8855pROCK 8855pROCK2 885–5p/ROCK circABCA1/miR885–5p/ROCK circABCA1miR8855pROCK ABCA1miR ABCAmiR miR88 8 8855pROCK miR8