Identification of the CeRNA axis of circ_0000006/miR-483-5p/KDM2B in the progression of aortic aneurysm to aorta dissection.

BACKGROUND: Aortic aneurysm (AA) and aortic dissection (AD) are serious cardiovascular disorders with a high risk of mortality. The molecular mechanisms underlying the progression from AA to AD are not well understood. This study aimed to identify the key circular RNA (circRNA)-microRNA (miRNA)-messenger RNA (mRNA) regulatory axis involved in this disease progression.

METHODS: CircRNA microarray, miRNA microarray, and mRNA sequencing were performed on plasma samples from healthy controls, AA patients, and AD patients. Bioinformatics analysis integrated the expression profiles to identify dysregulated circRNA-miRNA-mRNA networks. Key molecules were validated in vascular smooth muscle cells (VSMCs) and an AD mouse model. Cell proliferation, migration, and phenotypic transition assays were conducted after modulating the identified circRNA. The impact on AD progression was evaluated in mice upon circRNA knockdown.

RESULTS: A total of 12 circRNAs were found upregulated in AD compared to AA samples. miR-483-5p was downregulated while its targets KDM2B and circ_0000006 were upregulated in AD. Silencing circ_0000006 in VSMCs inhibited PDGF-induced phenotypic switching, proliferation, and migration by increasing miR-483-5p and decreasing KDM2B levels. In the AD mouse model, knockdown of circ_0000006 alleviated disease progression with similar molecular changes.

CONCLUSION: The study identified a novel circ_0000006/miR-483-5p/KDM2B axis dysregulated during AD progression. Targeting this axis, especially circ_0000006, could be a potential strategy to mitigate the transition from AA to AD by modulating VSMC phenotype and function.