Obstructive Sleep Apnea-induced Endothelial Dysfunction is Mediated by miR-210.
Fenqing ShangShen-Chih WangBrendan GongolSo Yun HanYoshitake ChoCara R SchiavonLili ChenYuanming XingYingshuai ZhaoMing'an NingXuan GuoFangzhou HeYuyang LeiLiuyi WangUri ManorTraci MarinKun-Ta ChouMing HePo-Hsun HuangJohn Y-J ShyyAtul MalhotraPublished in: American journal of respiratory and critical care medicine (2022)
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.
Keyphrases
- artificial intelligence
- obstructive sleep apnea
- big data
- cell proliferation
- long non coding rna
- deep learning
- long noncoding rna
- positive airway pressure
- blood pressure
- rna seq
- mouse model
- single cell
- heart failure
- gene expression
- dna methylation
- endothelial cells
- oxidative stress
- binding protein
- risk assessment
- adipose tissue
- skeletal muscle
- electronic health record
- climate change
- cell free
- circulating tumor
- microbial community
- insulin resistance
- hypertensive patients
- wastewater treatment
- newly diagnosed