Coronary microvascular dysfunction, Single-cell RNA sequencing, Bioinformatics analysis, Endothelial cells, Endothelial-to-mesenchymal transition, Medicine, Science

Abstract Coronary microvascular dysfunction serves as one of the etiological factors for ischemic heart disease and represents a novel therapeutic direction for coronary artery diseases; however, the research on its pathogenesis remains inconsistent. This study aims to explore the single-cell gene expression profiles in rats with coronary microvascular dysfunction using single-cell RNA sequencing, with a particular focus on the in-depth analysis of endothelial cell gene expression characteristics. By establishing a rat model of coronary microvascular dysfunction, we collected cardiac apical tissue to prepare single-cell suspensions and further analyzed them using bioinformatics methods. From a total of 55,419 cells, we identified 28 distinct cell clusters, with endothelial cells and fibroblasts being the predominant cell types. Compared to the NC group, the proportion of endothelial cells in the CMD group was significantly reduced, while the number of fibroblasts was significantly increased. Through further analysis of the endothelial cells, we classified them into normal phenotype endothelial cells, mesenchymal phenotype endothelial cells, proliferative phenotype endothelial cells, and lymphatic endothelial cells, with mesenchymal and proliferative endothelial cells originating from normal phenotype endothelial cells. Additionally, the CMD group exhibited an increase in immune cells, enhanced inflammatory response, and increased oxidative stress. These findings may provide novel potential therapeutic targets for the treatment of Coronary microvascular dysfunction.