Mapping the Cell-Cell Interactions in Cardiovascular Diseases: A Single-Cell Atlas Perspective

Cell-cell interactions play a critical role in maintaining cardiovascular homeostasis by coordinating communication among cardiomyocytes, endothelial cells, fibroblasts, smooth muscle cells, and immune cells. In cardiovascular disease (CVD), these interactions become dysregulated, driving inflammation, fibrosis, endothelial dysfunction, and adverse remodeling. Recent advances in single-cell and spatial transcriptomics have enabled the construction of detailed cellular atlases of the human heart and vasculature, allowing systematic inference of intercellular communication through ligand-receptor analysis. These efforts have uncovered disease-specific alterations in key signaling pathways. In this review, we summarize the major changes in intercellular communication observed across diverse cardiovascular pathologies. We highlight how altered crosstalk among vascular, stromal, and immune cells contributes to cardiomyopathy, myocardial infarction and heart failure. Understanding these disrupted signaling networks provides new insights into the molecular mechanisms of CVD and may guide the development of targeted therapies aimed at restoring healthy cell-cell communication.