Atrial fibrillation (AF) is a common arrhythmia in the clinic. Ablation failure and recurrence after cardioversion have become medical problems worldwide. An important pathological feature of AF is atrial fibrosis, which increases susceptibility to AF. As an important target of fibrosis signal integration, the signal transducer and activator of transcription 3 (STAT3) signaling pathway plays an important role in fibrosis. Caveolin-1 (CAV1), a cell membrane protein, is involved in a variety of the biological functions of cells. However, the role of CAV1 in atrial fibrosis remains unclear. In this study, Masson's trichrome staining was used to detect the degree of atrial fibrosis, and the expression of CAV1 in the human atrium was evaluated by immunohistochemistry. To further study the role of CAV1, its expression in cultured rat atrial fibroblasts was silenced using siRNAs. Atrial fibroblasts were treated with angiotensin II to observe the effects on CAV1 and the transforming growth factor-β1 and STAT3 signaling pathways. We also detected the effects of CAV1 scaffolding domain (CSD) peptide on fibrosis through the addition of exogenous CSD peptide. The results showed that CAV1 expression decreased with the aggravation of atrial fibrosis and that this effect increased the incidence of AF. The depletion of CAV1 induced excessive extracellular matrix deposition by activating the STAT3 and transforming growth factor-β1/SMAD2 signaling pathways, and this effect was exacerbated by stimulation with angiotensin II and improved by CSD peptide. These data suggested that CAV1 not only plays a critical role in fibrosis progression but also provides a target for the treatment of atrial fibrosis and AF.

中文翻译：

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Caveolin-1 缺乏通过 STAT3 信号通路诱导心房纤维化并增加对心房颤动的易感性。

心房颤动（AF）是临床上常见的心律失常。复律后消融失败和复发已成为世界范围内的医学问题。房颤的一个重要病理特征是心房纤维化，增加了房颤的易感性。作为纤维化信号整合的重要靶点，信号转导和转录激活因子3（STAT3）信号通路在纤维化中发挥着重要作用。Caveolin-1 (CAV1) 是一种细胞膜蛋白，参与细胞的多种生物学功能。然而，CAV1 在心房纤维化中的作用仍不清楚。本研究采用Masson三色染色检测心房纤维化程度，免疫组化评价CAV1在人心房中的表达。为了进一步研究 CAV1 的作用，使用 siRNA 使其在培养的大鼠心房成纤维细胞中的表达沉默。用血管紧张素II处理心房成纤维细胞以观察对CAV1和转化生长因子-β1和STAT3信号通路的影响。我们还通过添加外源 CSD 肽检测了 CAV1 支架结构域 (CSD) 肽对纤维化的影响。结果表明，随着心房纤维化的加重，CAV1的表达降低，这种作用增加了AF的发生率。CAV1 的耗竭通过激活 STAT3 和转化生长因子-β1/SMAD2 信号通路诱导过度的细胞外基质沉积，这种作用因血管紧张素 II 刺激而加剧，而 CSD 肽可改善这种作用。