He Yang-Zhi-Ge, Wang Yi-Xuan, Ma Jing-Si, Li Ruo-Nan, Wang Jia, Lian Tian-Yu, Zhou Yu-Ping, Yang Hao-Pu, Sun Kai, Jing Zhi-Cheng
Center for bioinformatics, National Infrastructures for Translational Medicine, Institute of Clinical Medicine & Chinese Academy of Medical Sciences and Peking Union Medical College Hospital, Beijing 100730, China.
Laboratory Department of Qingzhou People's Hospital, Qingzhou 262500, Shandong, China.
Vascul Pharmacol. 2023 Dec;153:107216. doi: 10.1016/j.vph.2023.107216. Epub 2023 Sep 10.
Pulmonary arterial hypertension (PAH) is a complex and progressive disease characterized by pulmonary arterial remodeling. Despite that current combination therapy has shown improvement in morbidity and mortality, a better deciphering of the underlying pathological mechanisms and novel therapeutic targets is urgently needed to combat PAH. MicroRNA, the critical element in post-transcription mechanisms, mediates cellular functions mainly by tuning downstream target gene expression. Meanwhile, upstream regulators can regulate miRNAs in synthesis, transcription, and function. In vivo and in vitro studies have suggested that miRNAs and their regulators are involved in PAH. However, the miRNA-related regulatory mechanisms governing pulmonary vascular remodeling and right ventricular dysfunction remain elusive. Hence, this review summarized the controversial roles of miRNAs in PAH pathogenesis, focused on different miRNA-upstream regulators, including transcription factors, regulatory networks, and environmental stimuli, and finally proposed the prospects and challenges for the therapeutic application of miRNAs and their regulators in PAH treatment.
肺动脉高压（PAH）是一种以肺动脉重塑为特征的复杂的进行性疾病。尽管目前的联合治疗已显示出发病率和死亡率有所改善，但迫切需要更好地解读其潜在的病理机制并确定新的治疗靶点以对抗PAH。微小RNA（MicroRNA）是转录后机制中的关键要素，主要通过调节下游靶基因的表达来介导细胞功能。同时，上游调节因子可在合成、转录和功能方面调控微小RNA。体内和体外研究表明，微小RNA及其调节因子与PAH有关。然而，控制肺血管重塑和右心室功能障碍的微小RNA相关调节机制仍不清楚。因此，本综述总结了微小RNA在PAH发病机制中的争议性作用，重点关注了不同的微小RNA上游调节因子，包括转录因子、调节网络和环境刺激，最后提出了微小RNA及其调节因子在PAH治疗中的治疗应用前景和挑战。
