Abstract

Heart failure is a significant public health challenge, persisting as a prime contributor to mortality and morbidity. Autophagy, as a cellular process, plays a crucial role in maintaining an optimal intracellular environment and holds therapeutic potential in the context of heart failure, but the correlation between autophagy and heart failure has yet to be fully elucidated. Single cell ribonucleic acid sequencing is a powerful method for investigating cell-specific transcriptome changes in heart failure. The study aimed to find autophagy-related molecules, mechanisms, and pathways at the single-cell level. Additionally, we sought to assess the prognostic implications for individuals with heart failure. First, we downloaded the heart failure related datasets from the Gene Expression Omnibus database to identify autophagy-related differential genes. We identified 9 cell-specific transcriptional signatures associated with autophagy that might be involved in heart failure progression, and the expression of these genes was detected by single-cell strategy. Correlation analysis revealed the relationships between these genes and the expression patterns of various immune cell types. The results of functional enrichment analysis revealed a strong association of autophagy-related genes with cellular responses to external stimuli, as well as significant enrichment in lipid metabolism, atherosclerosis, and the phosphoinositide 3-kinase/protein kinase B signaling pathway. Potential targets were predicted by protein-protein interaction and molecular docking. This study has yielded novel insights into the role of autophagy-related cell-type-specific expression genes as biomarkers in the pathogenesis of heart failure, and established a valuable resource for further investigations into the underlying molecular mechanisms.