WTAP affects intracranial aneurysm progression by regulating m6A methylation modification

Area of Science:

• Biochemistry
• Molecular Biology
• Vascular Biology

Background:

• Intracranial aneurysm (IA) is a cerebrovascular disease affecting the circle of Willis.
• Aberrant N6-methyladenosine (m6A) RNA methylation is implicated in various diseases.
• WTAP protein is crucial for recruiting m6A methyltransferase complexes and correlates with m6A levels.

Purpose of the Study:

• To investigate the role of m6A methylation mechanisms in the pathogenesis of intracranial aneurysms.
• To explore the specific involvement of WTAP in the cellular response to IA-related stimuli.

Main Methods:

• Established a rat model of intracranial aneurysm using selective arterial ligation.
• Quantified m6A levels and m6A-related gene expression in blood and brain samples.
• Utilized TNF-α to induce rat brain microvascular endothelial cells (rBMVECs) and assessed WTAP's effects in vitro.

Main Results:

• IA rats exhibited significantly reduced m6A RNA methylation in blood and circle of Willis samples.
• WTAP expression was downregulated, while ALKBH1 was upregulated in IA rat samples and TNF-α-treated rBMVECs.
• WTAP overexpression counteracted TNF-α-induced inhibition of rBMVEC viability and apoptosis.

Conclusions:

• Reduced m6A methylation and altered WTAP/ALKBH1 expression are associated with intracranial aneurysm.
• WTAP overexpression mitigates the detrimental effects of TNF-α on brain microvascular endothelial cells.
• WTAP may serve as a protective factor in intracranial aneurysms by modulating m6A methylation.