Delineating the Role of ITGAM in Macrophage Dynamics and Cardiac Modulation during Sepsis-Induced Cardiomyopathy

Abstract

BackgroundSepsis-induced cardiomyopathy (SIC) represents a critical complication of sepsis, characterized by reversible myocardial dysfunction and alterations. Despite extensive research, the molecular mechanisms underlying SIC remain poorly understood. MethodsUtilizing bioinformatics analysis of RNA-seq and scRNA-seq data from the GEO database, we identified key immune cell populations and molecular markers associated with SIC. Our in vitro and in vivo studies focused on the roles of ITGAM and ICAM-1 in macrophage recruitment and transformation as well as the impact of these changes on cardiac function. ResultsBioinformatics analysis revealed significant alterations in gene expression and immune cell composition in cardiac tissue during SIC, with macrophages being the predominant immune cell type. ITGAM was identified as crucial molecule in this process. In vitro experiments demonstrated an upregulation of ITGAM in macrophages and ICAM-1 in endothelial cells following LPS stimulation, indicating their roles in immune cell recruitment and interaction. Furthermore, the use of ITGAM-neutralizing antibodies led to reduced macrophages infiltration and initially improved cardiac function in SIC mice, but resulted in increased mortality in later stages. These findings highlight the dual role of ITGAM in SIC, facilitating early-stage inflammation and later-stage cardiac recovery. ConclusionThis study elucidates the complex dynamics of immune cells in SIC, with a particular emphasis on the role of ITGAM in macrophage modulation. The findings provide new insights into the reversible nature of myocardial dysfunction in SIC and underscore the importance of targeted therapeutic strategies for effective sepsis management. HighlightsIdentifies ITGAM as a key modulator in macrophage dynamics during sepsis-induced cardiomyopathy (SIC). Elucidates the impact of ITGAM on cardiac function in SIC. Reveals new insights into the immune-cellular mechanisms in SIC pathology.