Integrative Single‐Cell Analysis Dissects the Transcriptomic Remodeling and Altered Interaction Networks of Endothelial Cells During Myocardial Infarction

Myocardial infarction (MI) is a cardiovascular disease characterized by the irreversible necrosis of myocardial cells and high morbidity and mortality rates. The vascular contributions and diversity of endothelial cells in this fatal disease are poorly characterized. Here, we integrated multiple mouse cardiac single-cell transcriptomic data from six time points after MI and characterized the transcriptome reprogramming of endothelial cell subsets. Endothelial cell subsets differentiation trajectory analysis was conducted using scVelo, CellRank, and Dynamo. In silico simulation of Sox17 depletion perturbed the phenotypic transition from tip-like cells to capillary endothelial cells. Endothelial cell and immune cell interaction analyses identified a Mif-Cd44 interaction between tip-like cells and monocytes in the acute phase. In vivo pharmacological inhibition of Mif exacerbated cardiac dysfunction in the mouse MI model.