The underlying mechanism of cardiac injury in exertional heat stroke rats based on the scRNA-seq analysis

Abstract

Background Heat dissipation relies on an intact cardiovascular system to dilate cutaneous blood vessels and increase cardiac output. However, the heart becomes a vulnerable organ and is susceptible to cardiac arrhythmias, functional failure, and focal myocardial necrosis in a hyperthermic heat-damaged state. In particular, people with cardiovascular dysfunction are at a much higher risk of exertional heat stroke (EHS). This study aimed to investigate and validate the cell signaling pathways and key genes associated with EHS by analyzing single-cell RNA sequencing (scRNA-seq) data from cardiac apical tissue of EHS rats. The findings are intended to elucidate the mechanisms underlying cardiac injury and to provide a theoretical basis for the early identification of biomarkers for cardiac injury in EHS. Results After exertional heat radiation, the heart's functionality was compromised. Annotation analysis revealed that the cell type and quantity did not differ between the EHS and control (CTL) groups. Cellchat analysis showed that the signal of EHS cardiac apex cells was enhanced in chemokine signaling pathway. The cardiac apical cells of the EHS group had the highest number of enriched genes in the oxidative stress pathway, according to GO/KEGG analysis of endothelial cells with the biggest proportion of cells. A total of 310 genes with changes in expression between the two groups were evaluated based on the Seurat-FindAllMarkers tools for all cell types. Of these, 18 genes with substantial variability were chosen for further verification. By using RT-qPCR verification, the expression differences of 12 genes were confirmed to be consistent with the above bioinformation analysis. Finally, Additional immunohistochemistry tests verified that Hspa8 and Hspe1 were up-regulated once more, while Id1, Ndufa4, and Cd36 were down-regulated. Conclusions The gene expression levels of Id1, Ndufa4, Cd36 were significantly reduced, and Hspa8, Hspe1 were significantly increased. These screened hypervariable genes play different roles in heat stress-induced mitochondrial and myocardial mechanical damage, protein misfolding, and they may become potential biomarkers in the mechanism of cardiac injury or keep an important link in the functional pathway of action described above.