Department of Cardiology, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, China.
Department of General Medicine, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, China.
Biomolecules. 2024 Aug 25;14(9):1053. doi: 10.3390/biom14091053.
Atrial fibrillation (AF) is the most common sustained arrhythmia to affect 1% of the global population and increases with age. Atrial fibrosis is a crucial substrate for promoting structural remodeling to cause atrial arrhythmogenesis. Bone morphogenic protein 2 (BMP2) has been reported to be involved in cardiac fibrogenesis. However, its role in modulating atrial fibrosis to affect AF development remains unknown. Our study aimed to investigate the expression of BMP2 under different AF conditions and the effect of BMP2 on the progression of atrial fibrosis using an angiotensin II (Ang II) rat model and an ex vivo cardiac fibroblast model. The qRT-PCR and Western blot assay showed increased mRNA and protein levels in the atria of chronic AF patients and the right atria of a tachypacing rabbit model. In contrast, the levels of BMP2 receptor mRNA were comparable. The AF incidence of the Ang II rat was higher than that of a control rat, which was reduced by BMP2 treatment. Masson staining demonstrated an anti-fibrogenic impact on BMP2-subjected rat atria compared to only Ang II-treated rat atria. RNA-sequencing indicated the potential function of blocking NLRP3-associted inflammasome activation in BMP2-treated rat atrial tissues. In vitro, transfecting BMP2 shRNA into neonatal rat atrial fibroblasts upregulated the mRNA levels of and the secretion of IL-1β and IL-6. In contrast, recombinant BMP2 protein attenuated the increased levels of the NLRP3 inflammasome pathway induced by Ang II. In summary, BMP2 opposes atrial fibrosis to alleviate AF susceptibility by inhibiting the activation of the inflammasome in atrial fibroblasts.
心房颤动（AF）是最常见的持续性心律失常，影响全球 1%的人群，并随着年龄的增长而增加。心房纤维化是促进结构重塑导致心房心律失常发生的关键基质。骨形态发生蛋白 2（BMP2）已被报道参与心肌纤维化。然而，其在调节心房纤维化以影响 AF 发展中的作用尚不清楚。我们的研究旨在探讨不同 AF 条件下 BMP2 的表达以及 BMP2 对血管紧张素 II（Ang II）大鼠模型和离体心脏成纤维细胞模型中心房纤维化进展的影响。qRT-PCR 和 Western blot 分析显示，慢性 AF 患者的心房和快速起搏兔模型的右心房中 mRNA 和蛋白水平升高，而 BMP2 受体 mRNA 水平相当。Ang II 大鼠的 AF 发生率高于对照组大鼠，而 BMP2 治疗可降低其发生率。Masson 染色显示，与仅接受 Ang II 处理的大鼠心房相比，BMP2 处理的大鼠心房具有抗纤维化作用。RNA 测序表明，BMP2 处理的大鼠心房组织中可能通过阻断 NLRP3 相关炎性小体激活来发挥作用。在体外，将 BMP2 shRNA 转染到新生大鼠心房成纤维细胞中可上调 mRNA 水平和 IL-1β和 IL-6 的分泌。相反，重组 BMP2 蛋白可减轻 Ang II 诱导的 NLRP3 炎性小体通路水平升高。总之，BMP2 通过抑制心房成纤维细胞中炎性小体的激活来拮抗心房纤维化，从而减轻 AF 的易感性。
