Front Immunol. 2026 Jul 9;17:1901792. doi: 10.3389/fimmu.2026.1901792. eCollection 2026.
ABSTRACT
Obstructive sleep apnea (OSA) is increasingly recognized as an independent contributor to atherosclerotic cardiovascular disease, yet the mechanisms linking nocturnal intermittent hypoxia (IH) to plaque progression remain incompletely understood. Beyond oxidative stress and sympathetic activation, emerging evidence suggests that the gut may function as a critical relay organ between OSA and vascular injury. IH reshapes the intestinal ecosystem by altering microbial composition, weakening epithelial and mucus barrier integrity, and remodeling microbial metabolites, thereby increasing systemic exposure to microbial ligands and potentially pro-atherogenic metabolic signals, while reducing protective short-chain fatty acids. Trimethylamine N-oxide(TMAO) and imidazole propionate (ImP) are discussed as representative microbiota-derived metabolites implicated in atherosclerosis, although direct evidence linking OSA-related IH to increased circulating TMAO in human cohorts remains limited. These intestinal inflammatory and metabolic inputs may amplify endothelial dysfunction, macrophage activation, and chronic vascular inflammation. We propose that PANoptosis, an integrated inflammatory cell death program involving pyroptosis, apoptosis, and necroptosis, may represent a plausible downstream inflammatory cell death mechanism through which dysbiosis-associated and plaque-local stressors converge to promote plaque injury. This review summarizes convergent indirect evidence supporting a gut dysbiosis-PANoptosis-vascular injury hypothesis, and discusses potential therapeutic implications for OSA-associated atherosclerosis.
PMID:42495605 | PMC:PMC13391299 | DOI:10.3389/fimmu.2026.1901792