Yu Yahan, Fan Zheyu, Han Yanna, Sun Xi, Dong Chaorun, Liu Guanqun, Yin Xinda, Liu Linhe, Bai Yunlong, Yang Baofeng
Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, People's Republic of China.
Zhuhai People's Hospital, Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Hospital Affiliated with Jinan University, Jinan University, Zhuhai, 519000, People's Republic of China.
J Cell Commun Signal. 2023 Sep;17(3):813-825. doi: 10.1007/s12079-023-00721-6. Epub 2023 Jan 24.
Atrial fibrillation (AF), one of the most common types of arrhythmias, is associated with high morbidity and mortality, seriously endangering human health. Inflammation is closely associated with AF development. Activation of the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome in cardiomyocytes has been shown to promote AF progression. Here, we demonstrate the effect of miR-135 on NLRP3 inflammasome and study the cardioprotective role of miR-135 in AF. We observed that overexpression of miR-135 in mice reduced the AF incidence and duration, and inhibited both excessive activation of NLRP3 inflammasome and the increased intracellular calcium release during AF. However, the inhibitory effect of miR-135 on AF was partly abolished in the presence of a specific agonist of the calcium-sensing receptor (CaSR). We showed in the present study that miR-135 has a protective effect against AF by suppressing intracellular calcium-mediated NLRP3 inflammasome activation, suggesting the potential of miR-135 as a therapeutic agent in the treatment of AF.
心房颤动（AF）是最常见的心律失常类型之一，与高发病率和死亡率相关，严重危及人类健康。炎症与AF的发生密切相关。已证明心肌细胞中核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）炎性小体的激活会促进AF进展。在此，我们展示了miR-135对NLRP3炎性小体的影响，并研究了miR-135在AF中的心脏保护作用。我们观察到，在小鼠中过表达miR-135可降低AF的发生率和持续时间，并抑制NLRP3炎性小体的过度激活以及AF期间细胞内钙释放的增加。然而，在存在钙敏感受体（CaSR）特异性激动剂的情况下，miR-135对AF的抑制作用部分被消除。我们在本研究中表明，miR-135通过抑制细胞内钙介导的NLRP3炎性小体激活对AF具有保护作用，提示miR-135作为AF治疗药物的潜力。
