Novel proteins associated with chronic intermittent hypoxia and obstructive sleep apnea: From rat model to clinical evidence

Abstract

Objective To screen for obstructive sleep apnea (OSA) biomarkers, isobaric tags for relative and absolute quantitation (iTRAQ)-labeled quantitative proteomics assay was used to identify differentially expressed proteins (DEPs) during chronic intermittent hypoxia (CIH). Method The iTRAQ technique was applied to compare DEPs in the serum of a CIH rat model and control group. Biological analysis of DEPs was performed using Gene Ontology and Kyoto Encyclopedia to explore related biological functions and signaling pathways. Enzyme-linked immunosorbent assay (ELISA) was performed to validate their expression in sera from patients with OSA and CIH rats. Results Twenty-three DEPs (fold change ≥1.2 or ≤0.833, p<0.05) were identified, and two DEPs (unique peptides>3 and higher coverage) were further verified by ELISA in the CIH rat model and OSA subject: apolipoprotein A-IV (APOA4, p<0.05) and Tubulin alpha-1A chain (TUBA1A, p<0.05). Both groups showed significant differences in the expression levels of DEPs between the CIH and control groups and the severe OSA and non-OSA groups. APOA4 was found to be upregulated and TUBA1A downregulated in both the sera from OSA patients and CIH rats, on comparing proteomics results with clinical results. There were two pathways that involved three DEPs, the mitogen-activated protein kinase (MAPK) signaling pathway (p<0.05) and cytokine-cytokine receptor interaction (p<0.05). Conclusion APOA4 and TUBA1A may be potential novel biomarkers for CIH and OSA, and may play an important role in the development of OSA complications.

Silencing MR-1 Protects against Myocardial Injury Induced by Chronic Intermittent Hypoxia by Targeting Nrf2 through Antioxidant Stress and Anti-Inflammation Pathways

“…Cardiovascular dysfunction has been described in many sleep apnea patients, including hypertension, coronary artery disease, myocardial fibrosis, atrial dilatation, and cardiac failure [ 17 ]. Numerous animal models have been developed for the study of hypoxia, of which the most widely used is the CIH model, which simulates the intermittent hypoxia that occurs in OSAHS [ 18 , 19 ]. Heart damage, the HW/BW ratio, or levels of BNP and ANP have been reported to be significantly increased in CIH animals or OSA patients [ 9 , 20 ].…”

Disorders of gut microbiota in children with Tetralogy of Fallot

“…Furthermore, it is worth noting that in the TOF group, the KEGG pathways of NF-κB signaling, oxidative phosphorylation, cytokinecytokine receptor interaction, and VEGF signaling were significantly enriched, but there were fewer pathways associated with ribosome biogenesis in eukaryotes and glutathione metabolism. There is a close relationship between hypoxia and the NF-κB signaling pathway, as well as cytokine-cytokine receptor interaction and the VEGF signaling pathway (41)(42)(43)(44). The NF-κB signaling pathway plays a crucial role in inflammation, immunity, cell proliferation, differentiation, and survival (45), as well as in intestinal homeostasis and diseases (46).…”

Hypoxia modeling techniques: A review

“…For one of the methods of its simulation is the overlap of the tracheotomy cannula, which is closed for at least 10 s (simulation of apnea). The rat model of the upper airway occlusion (тracheostomy implantation) is performed under anesthesia [ 130 ]. Tracheotomized and anesthetized rats were ventilated via a computer-controlled collapsible upper airway segment [ 131 ].…”