Atrial fibrillation (AF) seriously reduces the health and life quality of patients. It is necessary to explore the pathogenesis of AF and provide a new target for the treatment. Here, exosomes were identified using transmission electron microscopy and nanoparticle tracing analysis. Western blotting assay was performed to detect the expression of exosomal surface markers, extracellular matrix-related proteins, and IL-16. The expression of genes was measured using qRT-PCR. Flow cytometry was performed to examine the percentages of CD86- and CD163-positive macrophages. Besides, luciferase activity assay was performed to explore the combination between PVT1 and miR-145-5p and the combination between miR-145-5p and IL-16 3’UTR. The combination between PVT1 and miR-145-5p also was examined using RIP assay. In our study, we isolated human cardiac myocyte- (HCM-) derived exosomes successfully. Ang-II-treated HCM-derived exosomes (Ang-II-Exo) promoted M1 macrophage polarization. PVT1 was highly expressed in Ang-II-Exo. Ang-II-Exo induced macrophage to M1 polarization through transferring PVT1. Furthermore, our data showed that PVT1 increased the expression of IL-16 via sponging miR-145-5p. Finally, we proved that exosomal PVT1 could boost the extracellular matrix remodeling of atrial fibroblasts. Overall, our data demonstrated that Ang-II-Exo promoted the extracellular matrix remodeling of atrial fibroblasts via inducing M1 macrophage polarization by transferring PVT1. PVT1 facilitated M1 polarization macrophage via increasing IL-16 expression by sponging miR-145-5p. Our results provided a new evidence for PVT1 which might be a treatment target of AF.

中文翻译：

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血管紧张素 II 处理的心肌细胞通过转移外泌体 PVT1 调节 M1 巨噬细胞极化

心房颤动（AF）严重降低了患者的健康和生活质量。有必要探索AF的发病机制，为治疗提供新的靶点。在这里，使用透射电子显微镜和纳米颗粒示踪分析鉴定了外泌体。进行蛋白质印迹测定以检测外泌体表面标志物、细胞外基质相关蛋白和 IL-16 的表达。使用qRT-PCR测量基因的表达。进行流式细胞术以检查 CD86 和 CD163 阳性巨噬细胞的百分比。此外，进行荧光素酶活性测定以探索PVT1与miR-145-5p之间的组合以及miR-145-5p与IL-16 3'UTR之间的组合。PVT1 和 miR-145-5p 之间的组合也使用 RIP 测定法进行了检查。在我们的研究中，我们成功地分离了人心肌细胞（HCM-）衍生的外泌体。Ang-II 处理的 HCM 衍生的外泌体 (Ang-II-Exo) 促进了 M1 巨噬细胞极化。PVT1 在 Ang-II-Exo 中高度表达。Ang-II-Exo 通过转移 PVT1 诱导巨噬细胞向 M1 极化。此外，我们的数据显示 PVT1 通过海绵化 miR-145-5p 增加 IL-16 的表达。最后，我们证明了外泌体 PVT1 可以促进心房成纤维细胞的细胞外基质重塑。总体而言，我们的数据表明，Ang-II-Exo 通过转移 PVT1 诱导 M1 巨噬细胞极化来促进心房成纤维细胞的细胞外基质重塑。PVT1 通过海绵化 miR-145-5p 增加 IL-16 表达来促进 M1 极化巨噬细胞。我们的结果为 PVT1 提供了新的证据，它可能是 AF 的治疗目标。