Identification MYD88 as a candidate molecule of sodium overload-induced cell death in myocardial ischemia-reperfusion...

Myocardial ischemia-reperfusion (I/R) injury disrupts intracellular ion homeostasis, triggering intracellular sodium overload and ultimately leading to cell death. However, the specific molecular mechanisms driving this pathological process remain incompletely understood.

Weighted gene co-expression network analysis (WGCNA) was applied to myocardial I/R injury transcriptomic datasets from the GEO database to identify genes associated with sodium accumulation. Subsequently, three machine learning algorithms (LASSO, Random Forest, and Support Vector Machine) were integrated to further screen for core hub genes. Single-cell RNA sequencing (scRNA-seq) data were utilized to determine the cellular localization of these key genes, followed by in vivo validation using a murine myocardial I/R injury model.

WGCNA identified 11 candidate genes highly correlated with sodium accumulation. Further screening via machine learning algorithms pinpointed MYD88 and GPR35 as core genes. Single-cell analysis revealed that MYD88 was specifically upregulated in macrophages, suggesting that sodium overload might exacerbate myocardial I/R injury by mediating inflammatory responses. In vivo experiments confirmed a significant elevation of sodium ion concentration in myocardial tissues following I/R, accompanied by a marked upregulation of MYD88 expression.

This study confirms that myocardial I/R injury triggers sodium overload and identifies MYD88 as a candidate molecule closely associated with sodium overload-induced cell death (SOICD). These findings provide a novel perspective for further exploring the pathological mechanisms underlying myocardial I/R injury.