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

Aging (Albany NY). 2024 May 8;16(9):8320-8335. doi: 10.18632/aging.205821. Epub 2024 May 8.

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.

Keywords: LncRNA; apoptosis; exosome; intracranial aneurysm; phenotype switching.

MeSH terms

  • Apoptosis* / genetics
  • Case-Control Studies
  • Exosomes* / genetics
  • Exosomes* / metabolism
  • Female
  • Humans
  • Intracranial Aneurysm* / blood
  • Intracranial Aneurysm* / genetics
  • Intracranial Aneurysm* / metabolism
  • Intracranial Aneurysm* / pathology
  • Male
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Middle Aged
  • Myocytes, Smooth Muscle* / metabolism
  • Phenotype*
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Sodium-Potassium-Exchanging ATPase / genetics
  • Sodium-Potassium-Exchanging ATPase / metabolism

Substances

  • ATP1A1 protein, human