Circ-LRP6 Inhibits the Development and Progression of AAA Via miR-29a-3p/HIF-1α Axis.

Abstract

Background: At present, the research on the potential molecular mechanism of abdominal aortic aneurysm (AAA) is limited, which hinders the treatment of aneurysm and the development of drugs. CircRNA has been identified as a potential therapeutic target for diagnostic biomarkers in a variety of diseases. The purpose of this study was to explore the molecular mechanism of circLRP6 in AAA and to provide a theoretical basis for further clinical optimization of treatment.

Methods: The animal model and cell model of AAA were constructed, and the circLRP6 expression was verified by in situ hybridization and qRT-PCR. The effect of circLRP6 on cell viability was determined using CCK-8 and BrdU. The effects of circLRP6 on the cell cycle and apoptosis were determined by flow cytometry. In addition, the interaction of circLRP6 with miR-29a-3p and HIF-1α was verified by the luciferase reporter gene and RIP. HIF-1α or caspase 3 expression was detected by immunofluorescence or western blot analysis.

Results: Our previous results showed that the circLRP6 had reduced expression in AAA, and its overexpression significantly inhibited AngII-induced hAoSMC cell viability. In addition, bioinformatics prediction showed that there was a binding site between miR-29a-3p and circLRP6, showing a negative regulatory relationship in hAoSMC. In addition, the results of the luciferase reporter gene and RIP showed that the circLRP6 interacted with HIF-1α, and achieved effective treatment of AAA by inhibiting the miR-29a-3p/HIF-1α.

Conclusion: CircLRP6 effectively inhibited the development of AAA by inhibiting the miR- 29a-3p/HIF-1α, providing a theoretical basis for further clinical optimization of treatment.