Twelve circular RNAs were found to be upregulated in aortic dissection (AD) compared to aortic aneurysm (AA) samples.
miR-483-5p was downregulated in AD, while its targets KDM2B and circ_0000006 were upregulated.
Silencing circ_0000006 in vascular smooth muscle cells inhibited key processes associated with disease progression.
In an aortic dissection mouse model, knocking down circ_0000006 reduced disease progression and induced similar molecular changes.
Simplified
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 ()-microRNA ()-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.
Key numbers
12
Upregulated in AD vs. AA
Number of found upregulated in AD samples compared to AA samples.
4 of 4
Patients in Each Group
Number of patients with AA and AD included in the study.
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Declarations. Ethics approval and consent to participate: The study was approved by the medical research committee of Affiliated Hospital of North Sichuan Medical College. All the subjects signed the informed consent. The animal protocol was approved by the animal use and welfare Committee of Affiliated Hospital of North Sichuan Medical College (No. 2023ER-114-1). The relevant experiments comply with the Declaration of Helsinki and the ARRIVE guidelines. Consent for publication: All authors approved the final version of the manuscript and agreed to this publication. Competing interests: The authors declare no competing interests.
