LncRNA XIST shuttled by adipose tissue-derived mesenchymal stem cell-derived extracellular vesicles suppresses myocardial pyroptosis in atrial fibrillation by disrupting miR-214-3p-mediated Arl2 inhibition.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

The mechanisms underlying atrial fibrillation (AF), a type of heart arrhythmia, have not been fully identified. Long noncoding RNAs (lncRNAs) have been implicated in the progression of AF. The current study aimed to ascertain the means by which X-inactive specific transcript (XIST), a lncRNA, contributes to the pathogenesis of AF in an animal model or in atrial myocytes. Extracellular vesicles (EVs) derived from mouse adipose tissue-derived mesenchymal stem cells (AMSCs) were isolated, transfected with XIST, and either injected into AF mouse models or incubated with atrial myocytes. The in vitro and in vivo effects of EV-derived XIST on myocardial pyroptosis were determined by Western blot analysis of pyroptosis-related protein and an ELISA for inflammatory factors. Bioinformatics analysis revealed a relationship between XIST, microRNA (miR)-214-3p, and Arl2, which was subsequently verified by a dual luciferase assay and RNA immunoprecipitation. Functional experiments were performed to elucidate whether changes in miR-214-3p or Arl2 regulated the effect of XIST on myocardial pyroptosis. Overexpressed XIST from AMSC-EVs were found to decrease myocardial pyroptosis while alleviating inflammation, which was demonstrated by reduced expression of nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like prot

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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