Unveiling the inflammatory link: integrated analysis identifies BMP7 and PPBP as key genes in obstructive sleep...

Obstructive sleep apnea (OSA) is an independently modifiable risk factor for atrial fibrillation (AF). However, the molecular mechanism of OSA-related AF is elusive. This study aims to identify the key genes and pathophysiological changes underlying OSA-related AF.

Three AF expression datasets, along with one OSA-related PBMC dataset and one OSA-related adipose tissue dataset, were acquired from the GEO database. DEG analysis and WGCNA were conducted to identify key AF-associated genes and OSA-related secretory proteins. PPI network analysis, functional enrichment, and cMAP were employed to uncover pathogenic genes, explore underlying mechanisms, and predict potential therapeutic compounds for OSA-related AF. LASSO regression and random forest were applied to screen candidate biomarkers and develop a diagnostic nomogram for OSA-related AF prediction. Immune cell infiltration in AF was assessed using the CIBERSORT algorithm. Finally, findings from bioinformatic analyses were validated through clinical cohort studies and animal model experiments.

The integrated AF dataset identified 123 AF key genes by intersecting differential expression and WGCNA. A total of 412 OSA-associated secretory proteins were screened by differential expression analysis of OSA-PBMC/adipose tissue datasets. PPI analysis identified two key modules containing 71 nodes, regarded as OSA-related AF pathogenic genes, which were mostly enriched in inflammatory and immune regulation by enrichment analysis. The cMAP analysis identified GW-9662 as a potential drug for OSA-related AF treatment. Six genes were overlapped between AF key genes and OSA-associated secretory proteins, and two hub genes were chosen as candidate biomarkers for developing nomogram with ideal diagnostic performance through machine learning. Immune cell infiltration results uncovered immune dysregulation in AF, and BMP7/PPBP were significantly associated with infiltrating immune cells. Finally, clinical and rat model validation confirmed that PPBP was upregulated and BMP7 downregulated in OSA with AF. A nomogram incorporating these genes showed good diagnostic performance (AUC = 0.843), and OSA rats exhibited increased AF susceptibility, fibrosis, and inflammation.

This study suggests that the downregulated BMP7 and upregulated PPBP may serve as key molecular features in the pathogenesis of OSA-related AF, highlighting a shared pathological pathway between OSA and AF.