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

Area of Science:

• Molecular Biology
• Cardiovascular Research
• Biochemistry

Background:

• Abdominal aortic aneurysm (AAA) pathogenesis remains poorly understood, limiting effective therapeutic strategies.
• Circular RNAs (circRNAs) are emerging as key regulators in various diseases and potential diagnostic biomarkers.
• Limited research exists on the molecular mechanisms underlying AAA, highlighting the need for novel insights.

Purpose of the Study:

• To investigate the molecular mechanism of circLRP6 in the context of abdominal aortic aneurysm (AAA).
• To explore circLRP6 as a potential therapeutic target for AAA.
• To provide a theoretical foundation for optimizing clinical treatments for AAA.

Main Methods:

• Construction of animal and cell models for AAA.
• Verification of circLRP6 expression using in situ hybridization and qRT-PCR.
• Assessment of cell viability, cell cycle, and apoptosis via CCK-8, BrdU, and flow cytometry.
• Confirmation of circLRP6 interactions with miR-29a-3p and HIF-1α using luciferase reporter gene and RIP assays.
• Detection of HIF-1α and caspase 3 expression through immunofluorescence and western blot analysis.

Main Results:

• Reduced circLRP6 expression was observed in AAA models.
• Overexpression of circLRP6 significantly inhibited AngII-induced human aortic smooth muscle cell (hAoSMC) viability.
• Bioinformatics and experimental validation confirmed a negative regulatory interaction between circLRP6 and miR-29a-3p in hAoSMCs.
• circLRP6 was found to interact with HIF-1α, collectively inhibiting the miR-29a-3p/HIF-1α axis to achieve effective AAA treatment.

Conclusions:

• CircLRP6 plays a crucial role in inhibiting AAA progression.
• The inhibitory effect of circLRP6 on AAA is mediated through the suppression of the miR-29a-3p/HIF-1α pathway.
• These findings offer a theoretical basis for the clinical optimization of AAA treatment strategies.