Abstract
OBJECTIVE: To explore the specific mechanism by which circ_0084043/miR-31-5p regulates high mobility group AT-hook 1 (HMGA1) and thus participates in atherosclerosis (AS). METHODS: Carotid plaque tissues, diseased vascular tissue, and corresponding normal tissue from areas adjacent to the plaques were collected from 49 AS patients between September 2020 and September 2023. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to determine circ_0084043 expression. The proliferation, migration, and invasion of vascular smooth muscle cells (VSMCs) induced by oxidized low-density lipoprotein (ox-LDL) were determined by CCK-8, clone formation, scratch, and Transwell assays. The targeted regulatory relationship among circ_0084043, miR-31-5p, and HMGA1 was verified by bioinformatics and dual luciferase reporter gene assay. An AS mouse model was established, and the pathological lesions in the aorta of AS model mice were observed by oil red O and HE stainings. Biochemical testing was performed to assess blood lipids in venous blood. qRT-PCR was used to determine the expression of miR-31-5p and HMGA1. Immunohistochemistry was performed to assess the expression of HMGA1 and α-smooth muscle actin (α-SMA) in the aorta of the AS model mice. RESULTS: In AS patients, the expression levels of circ_0084043 and HMGA1 in carotid plaque tissues and diseased vascular tissues were elevated (P<0.05), while the expression level of miR-31-5p was decreased (P<0.05). The expression of circ_0084043 was negatively correlated with the expression of miR-31-5p (r=－0.3855, P=0.0062). HMGA1 expression was positively correlated with circ_0084043 expression (r=0.3317, P=0.0199), and negatively correlated with miR-31-5p (r=－0.3351, P=0.0186). MiR-31-5p had target binding sites for both circ_0084043 and HMGA1. Compared with the control group, the proliferation, clone formation, migration, and invasion abilities of the sh-NC group, the scramble group, the circ_0084043+miR-31-5p mimics group, the miR-31-5p inhibitor+sh-HMGA1 group, and the circ_0084043+sh-HMGA1 group increased (P<0.05). In contrast, the proliferation, clone formation, migration, and invasion abilities of the sh-0084043 group significant decreased compared to those of the sh-NC group (P<0.05). The proliferation, clone formation, migration, and invasion abilities of the miR-31-5p mimics group and the sh-HMGA1 group decreased compared with those of the scramble group (P<0.05). Compared with the sh-NC group, sh-0084043 group had decreased aortic lipid plaque and necrotic core areas (P<0.05). Total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and the expression levels of HMGA1 mRNA and protein and α-SMA decreased (P<0.05), while high-density lipoprotein cholesterol (HDL-C) and miR-31-5p expression levels increased (P<0.05). CONCLUSION: circ_0084043 promotes the proliferation and migration of VSMCs and promotes the progress of AS by inhibiting miR-31-5p and increasing the expression of HMGA1.