Abstract Rationale Obstructive sleep apnea (OSA) involves the occurrence of repeated airway collapse during sleep, causing intermittent hypoxia (IH), sleep fragmentation (SF), or both (IH+SF). OSA increases the risk of cardiometabolic diseases and poses a major public health and economic burden. Advanced high-throughput proteomics technologies are now a key approach enabling identification of novel disease mediators and potential diagnostic or therapeutic targets, including OSA. Comparative analyses of circulating proteomic alterations among various murine models of OSA are currently unavailable. This study aimed to characterize mouse plasma proteomic alterations after IH, SF, and IH+SF exposures to identify molecular mechanisms and putative targets. Methods Adult male mice (3 months old) were exposed to SF, IH, or IH+SF for 6 months along with sleep controls (SC). Plasma samples were treated with perchloric acid for protein depletion. Proteomic analyses were performed using Liquid Chromatography-Mass Spectrometry (LC-MS) in DIA-PASEF mode on a Bruker timsTOF Pro2 mass spectrometer. Data were processed in Spectronaut, using the UniProt Mus musculus database for spectral matching. Gene Ontology (GO) analysis, heatmaps, and volcano plots were used for data visualization and interpretation, along with protein-protein interaction (PPI) network analysis for each experimental group. Results LC-MS analysis detected an average of 750 proteins per sample. Compared with controls, 96 differentially expressed proteins (DEPs) were identified in the IH group, 166 in SF, and 128 in IH+SF. Heatmaps and volcano plots showed some aberrant clustering, with occasional overlap between experimental groups. A total of 39 proteins were consistently altered across all conditions. Functional enrichment analysis revealed that these congruent DEPs were primarily involved in cholesterol metabolism and in complement and coagulation cascades. These pathways are known to play a key role in OSA progression, and their activation may contribute to OSA-related morbidities, including inflammation and cellular damage. Conclusion Both distinct and overlapping proteomic changes emerge in OSA-related murine models. Proteins consistently altered across all experimental groups suggest dysregulation of cholesterol metabolism and coagulation pathways—mechanisms that may underlie the increased cardiometabolic risk associated with OSA. These findings highlight potential research avenues and therapeutic targets. This abstract is funded by: MARC
Khalyfa et al. (Fri,) studied this question.