Integrated Analysis Reveals S100a8/a9 Regulates Autophagy and Apoptosis through the MAPK and PI3K-AKT Signaling Pathway in the Early Stage of Myocardial Infarction.

Myocardial infarction (MI), a type of coronary heart disease, has had a significantly increased incidence in recent years. The balance of cardiomyocyte apoptosis and autophagy after MI is one of the main determinants of patient prognosis. Both affect myocardial fibrosis and ventricular remodeling and regulate cell survival. However, there are few studies on the regulation mechanism of cardiomyocyte autophagy and apoptosis in the early stage after MI. In this study, based on analyzing the scRNA-seq and mRNA-seq data of mice in the early stage of MI, we found that the expression of S100a8 and S100a9 increased first and then decreased in the early stage of MI, and their expression level changed with the number of neutrophils. Further, through the functional enrichment analysis of the differentially expressed genes, we found that S100a8 and S100a9 were simultaneously associated with autophagy and apoptosis and could regulate autophagy and apoptosis of cardiomyocytes through MAPK or PI3K-AKT signaling pathways. This study provides valuable insights for clarifying the pathogenesis of early stage MI and improving its early treatment.

The atlas of ACE2 expression in fetal and adult human hearts reveals the potential mechanism of heart-injured patients infected with SARS-CoV-2.

Numerous studies have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect host cells through binding to angiotensin I converting enzyme 2 (ACE2) expressing in various tissues and organs. In this study, we deeply analyzed the single-cell expression profiles of ACE2 in fetal and adult human hearts to explore the potential mechanism of SARS-CoV-2 harming the heart. The molecular docking software was used to simulate the binding of SARS-CoV-2 and its variant spike protein with ACE2. The genes closely related to ACE2 in renin-angiotensin system (RAS) were identified by constructing a protein-protein interaction network. Through the analysis of single-cell transcription profiles at different stages of human embryos, we found that the expression level of ACE2 in ventricular myocytes was increased with embryonic development. The results of single-cell sequencing analysis showed that the expression of ACE2 in ventricular myocytes was upregulated in heart failure induced by dilated cardiomyopathy compared with normal hearts. The upregulation of ACE2 increases the risk of infection with SARS-CoV-2 in fetal and adult human hearts. We also further confirmed the expression of ACE2 and ACE2-related genes in normal and SARS-CoV-2-infected human pluripotent stem cell-derived cardiomyocytes. In addition, the pathway analysis revealed that ACE2 may regulate the differently expressed genes in heart failure through calcium signaling pathway and Wnt signaling pathway.