Intracranial aneurysm circulating exosome-derived LncRNA ATP1A1-AS1 promotes smooth muscle cells phenotype switching and apoptosis

Abstract

Exosomal long non-coding RNAs (LncRNAs) play a crucial role in the pathogenesis of cerebrovascular diseases. However, the expression profiles and functional significance of exosomal LncRNAs in intracranial aneurysms (IAs) remain poorly understood. Through high-throughput sequencing, we identified 1303 differentially expressed LncRNAs in the plasma exosomes of patients with IAs and healthy controls. Quantitative real-time polymerase chain reaction (qRT-PCR) verification confirmed the differential expression of LncRNAs, the majority of which aligned with the sequencing results. ATP1A1-AS1 showed the most significant upregulation in the disease group. Importantly, subsequent in vitro experiments validated that ATP1A1-AS1 overexpression induced a phenotype switching in vascular smooth muscle cells, along with promoting apoptosis and upregulating MMP-9 expression, potentially contributing to IAs formation. Furthermore, expanded-sample validation affirmed the high diagnostic value of ATP1A1-AS1. These findings suggest that ATP1A1-AS1 is a potential therapeutic target for inhibiting IAs progression and serves as a valuable clinical diagnostic marker.