Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Oxid Med Cell Longev. 2021 Aug 25;2021:9987219. doi: 10.1155/2021/9987219. eCollection 2021.
A relationship between excess epicardial adipose tissue (EAT) and the risk of atrial fibrillation (AF) has been reported. Browning of EAT may be a novel approach for the prevention or treatment of AF by attenuating atrial fibrosis. Previous studies have identified microRNA-21 (miR-21) as a regulatory factor in atrial fibrosis. The present study examined the role of different subtypes of miR-21 in adipose browning and atrial fibrosis under hyperglycemic conditions. Wild type and miR-21 knockout C57BL/6 mice were used to establish a diabetic model via intraperitoneal injection of streptozotocin. A coculture model of atrial fibroblasts and adipocytes was also established. We identified miR-21-3p as a key regulator that controls adipocyte browning and participates in atrial fibrosis under hyperglycemic conditions. Moreover, fibroblast growth factor receptor (FGFR) 1, a direct target of miR-21-3p, decreased in this setting and controlled adipose browning. Gain and loss-of-function experiments identified a regulatory pathway in adipocytes involving miR-21a-3p, FGFR1, FGF21, and PPAR that regulated adipocyte browning and participated in hyperglycemia-induced atrial fibrosis. Modulation of this signaling pathway may provide a therapeutic option for the prevention and treatment of atrial fibrosis or AF in DM.
已有研究报道，心外膜脂肪组织（EAT）过多与心房颤动（AF）的风险之间存在关联。EAT 的褐色化可能是通过减轻心房纤维化来预防或治疗 AF 的一种新方法。先前的研究已经确定 microRNA-21（miR-21）是心房纤维化的调节因子。本研究探讨了在高血糖条件下，不同亚型的 miR-21 在脂肪褐色化和心房纤维化中的作用。使用野生型和 miR-21 敲除 C57BL/6 小鼠通过腹腔注射链脲佐菌素建立糖尿病模型。还建立了心房成纤维细胞和脂肪细胞的共培养模型。我们确定了 miR-21-3p 作为一个关键的调节剂，它可以控制脂肪细胞的褐色化，并参与高血糖条件下的心房纤维化。此外，成纤维细胞生长因子受体（FGFR）1 是 miR-21-3p 的直接靶标，在这种情况下其表达减少，并控制脂肪细胞的褐色化。获得和丧失功能实验确定了一个涉及 miR-21a-3p、FGFR1、FGF21 和 PPAR 的调节途径，该途径调节脂肪细胞的褐色化，并参与高血糖诱导的心房纤维化。该信号通路的调节可能为预防和治疗糖尿病中的心房纤维化或 AF 提供治疗选择。
