LncRNA PVT1 Facilitates Phenotypic Switching of Vascular Smooth Muscle Cells in Intracranial Aneurysms by Recruiting KDM1A to Reduce H3K9me2 Modification.

This study explores the differential expression of lncRNA PVT1 in intracranial aneurysms (IAs) and its role in the phenotypic switching of vascular smooth muscle cells (VSMCs). PVT1 and ALOX5 expressions in the serum of IA patients and healthy controls were detected by qRT-PCR. The diagnostic efficacy of PVT1 for IA was analyzed using the receiver operating curve (ROC). VSMCs were treated with H(2)O(2) to induce phenotypic switching. PVT1 expression was silenced in VSMCs, followed by the detection of cell viability, inflammatory factors (TNF-α, IL-1β, IL-6), as well as α-SMA, OPN, and MMP2. RIP confirmed the binding between PVT1 and KDM1A. The enrichment of KDM1A and H3K9me2 on ALOX5 promoter was analyzed by ChIP. PVT1 expression in IA patients was significantly elevated, and PVT1 expression was correlated with the size and location of IAs. H(2)O(2) induced VSMCs to transition from contractile cells to synthetic cells, intensified cellular inflammation, and upregulated PVT1 expression. Inhibition of PVT1 repressed VSMC phenotypic switching. PVT1 promoted ALOX5 expression by recruiting KDM1A to reduce H3K9me2 modification. In conclusion, PVT1 is highly expressed in IA patients and has high diagnostic value. PVT1 promotes VSMC phenotypic switching by recruiting KDM1A to reduce H3K9me2 modification and enhance ALOX5 expression.