The role of microRNAs in pathophysiology and diagnostics of metabolic complications in obstructive sleep apnea patients

Abstract

Obstructive sleep apnea (OSA) is one of the most common sleep disorders, which is characterized by recurrent apneas and/or hypopneas occurring during sleep due to upper airway obstruction. Among a variety of health consequences, OSA patients are particularly susceptible to developing metabolic complications, such as metabolic syndrome and diabetes mellitus type 2. MicroRNAs (miRNAs) as epigenetic modulators are promising particles in both understanding the pathophysiology of OSA and the prediction of OSA complications. This review describes the role of miRNAs in the development of OSA-associated metabolic complications. Moreover, it summarizes the usefulness of miRNAs as biomarkers in predicting the aforementioned OSA complications.

Keywords: OSA; diabetes; metabolic complications; metabolic syndrome; microRNA; obstructive sleep apnea.

Figure 1

Potential role of microRNAs in the pathophysiology of metabolic syndrome in obstructive sleep apnea patients. Obstructive sleep apnea in general affects miR -181a, -22-3p, -17-5p, and via chronic intermittent hypoxia miR-21-5p and -130. Downregulation of miR-181a causes upregulation of TRIL and leads to abdominal obesity. Downregulation of miRNA-22-3p is associated with high blood pressure due to targeting MECP2. Downregulation of miR-17-5p triggers abdominal obesity and insulin resistance via TXNIP upregulation. miR-21-5p downregulation leads to the upregulation of TLR4, thereby contributing to abdominal obesity. Upregulation of miRNA-130 stimulates PPAR-γ, predisposing to abdominal obesity, dyslipidemia, and insulin resistance. miR, microRNA; TRIL, TLR4 interactor with leucine-rich repeats; MECP2, methyl-CpG binding protein 2; TXNIP, thioredoxin interacting protein; TLR4, toll-like receptor 4; PPAR- γ, peroxisome proliferator-activated receptor gamma.

Figure 2

Possible role of microRNAs in the pathophysiology of diabetes mellitus and diabetic complications. Chronic intermittent hypoxia as the main consequence of obstructive sleep apnea affects miR-31 and -155, resulting in their downregulation, and miR-126, -181a, and -199a, leading to their upregulation. Dysregulation of microRNAs can predispose patients suffering both from OSA and DM to particular complications. Decreased level of SATB2 contributes to impaired bone remodeling and endothelial dysfunction. In turn, BDNF dysregulation is associated with diabetic nephropathy. Downregulation of the VEGF gene results in diabetic retinopathy development. Increased TP53 and PDCD4 lead to diabetic cardiomyopathy. Targeting EGR-1 and KLF6 can trigger diabetic nephropathy. An increase in SP1 is responsible for diabetic cataract. Another upregulated target, FGF7, can contribute to diabetic retinopathy development. Downregulation of AKT, IGF, and FGF-1 play important role in diabetic cardiomyopathy development. miR, microRNA; SATB2, special AT-rich sequence-binding protein 2; BDNF, brain-derived neurotrophic factor; VEGF, vascular endothelial growth factor; PDCD4, programmed cell death 4; TP53, tumor protein 53; EGR1, early growth response 1; KLF6, Kruppel-like factor 6; SP1, specific protein 1; FGF7, fibroblast growth factor 7; AKT, protein kinase B; IGF, insulin-like growth factor 1; FGF1, fibroblast growth factor 1.