Obstructive Sleep Apnea-induced Endothelial Dysfunction Is Mediated by miR-210.
Obstructive Sleep Apnea-induced Endothelial Dysfunction Is Mediated by miR-210.
复制标题
阻塞性睡眠呼吸暂停诱发的内皮功能障碍是由 miR-210 介导的。
DOI：
10.1164/rccm.202202-0394oc
复制
发表时间：
2023
影响因子：
24.7
通讯作者：
He,Mi
中科院分区：
文献类型：
--
作者：
Shang,Fenqing;Wang,Shen-Chih;Gongol,Brendoan;Han,SoYun;Cho,Yoshitake;Schiavon,CaraR;Chen,Lili;Xing,Yuanming;Zhao,Yingshuai;Ning,Ming'an;Guo,Xuan;He,Fangzhou;Lei,Yuyang;Wang,Liuyi;Manor,Uri;Marin,Traci;Chou,Kun-Ta;He,Mi
Rationale:Obstructive sleep apnea (OSA)–induced endothelial cell (EC) dysfunction contributes to OSA-related cardiovascular sequelae. The mechanistic basis of endothelial impairment by OSA is unclear.Objectives:The goals of this study were to identify the mechanism of OSA-induced EC dysfunction and explore the potential therapies for OSA-accelerated cardiovascular disease.Methods:The experimental methods include data mining, bioinformatics, EC functional analyses, OSA mouse models, and assessment of OSA human subjects.Measurements and Main Results:Using mined microRNA sequencing data, we found that microRNA 210 (miR-210) conferred the greatest induction by intermittent hypoxia in ECs. Consistently, the serum concentration of miR-210 was higher in individuals with OSA from two independent cohorts. Importantly, miR-210 concentration was positively correlated with the apnea–hypopnea index. RNA sequencing data collected from ECs transfected with miR-210 or treated with OSA serum showed a set of genes commonly altered by miR-210 and OSA serum, which are largely involved in mitochondrion-related pathways. ECs transfected with miR-210 or treated with OSA serum showed reducedo2rate, mitochondrial membrane potential, and DNA abundance. Mechanistically, intermittent hypoxia-induced SREBP2 (sterol regulatory element–binding protein 2) bound to the promoter region of miR-210, which in turn inhibited the iron–sulfur cluster assembly enzyme and led to mitochondrial dysfunction. Moreover, the SREBP2 inhibitor betulin alleviated intermittent hypoxia–increased systolic blood pressure in the OSA mouse model.Conclusions:These results identify an axis involving SREBP2, miR-210, and mitochondrial dysfunction, representing a new mechanistic link between OSA and EC dysfunction that may have important implications for treating and preventing OSA-related cardiovascular sequelae.
