CircRBM33 contributes to ECM remodeling via miR-4268/EPHB2 axis in abdominal aortic aneurysm

Background: Abdominal aortic aneurysm (AAA) is a complex vascular disease involving expansion of the abdominal aorta. extracellular matrix (ECM) remodelling is crucial to AAA pathogenesis, however, the specific molecular mechanism remains unclear. This study aimed to investigate differentially expressed cirRNAs (DEcircRNAs) involved in ECM remodeling of AAA.Materials and Methods: Transcriptome shotgun sequencing was used to analyse the DEcircRNAs between the AAA tissues and adjacent normal tissues. The expression of circRNAs in tissues and cells was validated using quantitative reverse transcription PCR (RT-qPCR). Overexpression of circRNA in vascular smooth muscle cells (VSMCs) was employed to explore its effect on ECM remodeling of AAA. Bioinformatic technology, luciferase reporter gene assay, RT-qPCR, and rescue experiment were employed to understand regulatory mechanism of circRNA.Results: We identified 65 DEcircRNAs in AAA tissues compare with adjacent normal tissues, including 30 up-regulated and 35 down-regulated circRNAs, which were mainly involved in inflammation and ECM-related functions and pathways. Moreover, circRBM33 was significantly increased in AAA tissues and VSMCs with AngII introduction compared with normal samples. Overexpression of CircRBM33 decreased the expression of EMT-related molecule tissue inhibitor of matrix metalloproteinases-1 (TIMP-1). Mechanistically, miR-4268 targeted binding to circRBM33 and inhibited the luciferase activity of circRBM33. The overexpression of circRBM33 induced the expression of EPHB2, and this effect is countered by miR-4268 mimics.Conclusion: CircRBM33 can regulate ECM remodeling via miR-4268/EPHB2 axis, leading to AAA progression.