APA
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Shang, F., Wang, S.-C., Gongol, B., Han, S. Y., Cho, Y., Schiavon, C. R., … Malhotra, A. (2022). Obstructive Sleep Apnea-induced Endothelial Dysfunction is Mediated by miR-210. American Journal of Respiratory and Critical Care Medicine.
Chicago/Turabian
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Shang, Fenqing, Shen-Chih Wang, Brendan Gongol, So Yun Han, Yoshitake Cho, Cara R. Schiavon, Lili Chen, et al. “Obstructive Sleep Apnea-Induced Endothelial Dysfunction Is Mediated by MiR-210.” American Journal of Respiratory and Critical Care Medicine (2022).
MLA
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Shang, Fenqing, et al. “Obstructive Sleep Apnea-Induced Endothelial Dysfunction Is Mediated by MiR-210.” American Journal of Respiratory and Critical Care Medicine, 2022.
BibTeX Click to copy
@article{fenqing2022a,
title = {Obstructive Sleep Apnea-induced Endothelial Dysfunction is Mediated by miR-210.},
year = {2022},
journal = {American Journal of Respiratory and Critical Care Medicine},
author = {Shang, Fenqing and Wang, Shen-Chih and Gongol, Brendan and Han, So Yun and Cho, Yoshitake and Schiavon, Cara R. and Chen, Lili and Xing, Yuanming and Zhao, Yingshuai and Ning, Ming'an and Guo, Xuan and He, F. and Lei, Yuyang and Wang, Liuyi and Manor, U. and Marin, Traci L. and Chou, K. and He, M. and Huang, Po‐Hsun and Shyy, J. and Malhotra, A.}
}
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 miRNA-seq data, we found that microRNA 210 (miR-210) conferred the greatest induction by intermittent hypoxia in ECs. Consistently, the serum level of miR-210 was higher in OSA individuals from two independent cohorts. Importantly, miR-210 level was positively correlated with the apnea-hypopnea index. RNA-seq 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 reduced oxygen consumption rate, mitochondrial membrane potential and DNA abundance. Mechanistically, intermittent hypoxia induced sterol regulatory element-binding protein 2 (SREBP2) 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.
