Circular RNA hsa_circ_0008433 drives vascular smooth muscle cell modulation in intracranial aneurysm pathogenesis.

Background: Intracranial aneurysm (IA) is a serious condition that can lead to a life-threatening rupture, often resulting in a hemorrhagic stroke. Vascular smooth muscle cell (VSMC) dysfunction is a critical factor in the pathogenesis of IA, yet the molecular mechanisms underlying this relationship are not yet fully understood. Recent studies suggest that circular RNAs (circRNAs) are involved in various vascular diseases. High-throughput sequencing identified hsa_circ_0008433 as significantly upregulated in IA tissues, especially in ruptured cases, suggesting a role in IA progression.

Objectives: To further investigate the potential effects of hsa_circ_0008433 on the rupture of human IA.

Material and methods: This study aimed to investigate the effects of hsa_circ_0008433 on IA rupture. We validated the expression of hsa_circ_0008433 in IA patient tissue samples through reverse transcription quantitative polymerase chain reaction (RT-qPCR), comparing ruptured and unruptured aneurysms. Human brain vascular smooth muscle cells (HBVSMCs) were utilized to establish overexpression and knockdown models for hsa_circ_0008433. Cell Counting Kit-8 (CCK-8) and wound healing assays were conducted to assess cell proliferation and migration, while western blotting was employed to measure VSMC phenotype markers including α-smooth muscle actin (α-SMA), smooth muscle protein 22-alpha (SM22α), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9).

Results: The RT-qPCR analysis confirmed that hsa_circ_0008433 was significantly upregulated in IA tissues, especially in ruptured samples (p < 0.05). Overexpression of hsa_circ_0008433 in HBVSMCs promoted proliferation, migration and phenotype switching, indicated by increased expression of MMPs and decreased contractile proteins. The effects were reversed by the knockdown of hsa_circ_0008433.

Conclusions: We have shown that hsa_circ_0008433 regulates vascular smooth muscle cell function and promotes behaviors that may lead to intracranial aneurysm instability. This study advances the understanding of the role of circRNAs in vascular pathology and identifies hsa_circ_0008433 as a potential therapeutic target for IA. These findings open opportunities for targeted treatments and broader applications in vascular disease research.