biostudies-literatureGuo ZThe Key projects of Qilu Hospital (Qingdao) Foundation41774https://www.ebi.ac.uk/biostudies/studies/S-EPMC12647232biostudies-literatureUnknown15(1)Intracranial aneurysm (IA) is a type of cerebrovascular complication that can result in subarachnoid hemorrhage. Published research have evidenced the involvement of METTL3, a critical mRNA m⁶A methyltransferase, in the generation of various cardiovascular diseases. However, its specific role in regulating IAs remains unclear. Our research demonstrated downregulation of METTL3 in IA patients and a significant positive correlation with AMPK expression. In vascular smooth muscle cells (VSMCs), overexpressing METTL3 led to an upregulation of contractile marker genes (SM-22α & α-SMA), while the expressions of TNF-α, IL-1β, iNOS, IL-6, MMP-9, and MMP-3 were significantly downregulated. This effect was reversed by the use of the AMPK inhibitor Compound C. Therefore, it can be postulatScientific reportsMETTL3 promotes vascular stability in intracranial aneurysm via m6A-AMPK axis.PMC12647232QDKY2020ZD01Guo ZZhong YWang YMing ZfalseMETTL3 promotes vascular stability in intracranial aneurysm via m6A-AMPK axis.Intracranial aneurysm (IA) is a type of cerebrovascular complication that can result in subarachnoid hemorrhage. Published research have evidenced the involvement of METTL3, a critical mRNA m⁶A methyltransferase, in the generation of various cardiovascular diseases. However, its specific role in regulating IAs remains unclear. Our research demonstrated downregulation of METTL3 in IA patients and a significant positive correlation with AMPK expression. In vascular smooth muscle cells (VSMCs), overexpressing METTL3 led to an upregulation of contractile marker genes (SM-22α & α-SMA), while the expressions of TNF-α, IL-1β, iNOS, IL-6, MMP-9, and MMP-3 were significantly downregulated. This effect was reversed by the use of the AMPK inhibitor Compound C. Therefore, it can be postulat2025-01-01T00:00:00Z2025 Nov2026-06-05T16:41:24.066Z2026-05-18T03:12:56.734ZS-EPMC126472324129074210.1038/s41598-025-25685-y