Objective: Although cellular heterogeneity within arterial walls has been explored in mice and nonhuman primates, the cellular composition of human arterial walls remains unclear. Approach and Results: The cellular composition of nondiseased cardiac arteries (3 aortas, 2 pulmonary arteries and 9 coronary arteries) from 3 heart transplantation patients were investigated by single-cell sequencing of >10 5 cells. Clustering analysis identified 25 subpopulations representing the 10 main arterial cell types: vascular smooth muscle cell (4 clusters), fibroblast (4 clusters), macrophage (Mφ, 4 clusters), T cell (4 clusters), endothelial cell (4 clusters), NK cell (2 clusters), mast cell (1 cluster), myofibroblast (1 cluster), oligodendrocyte (1 cluster), and B/plasma cells (1 cluster). Vascular smooth muscle cell was the largest cell population in cardiac arteries, followed by fibroblast, Mφ, T cell, endothelial cell, NK cell, and so on. We compared cellular composition among different arteries and found some artery-specific vascular smooth muscle cell and fibroblast subpopulations. The communication between vascular smooth muscle cell and fibroblast was predominant in nondiseased condition. Atherosclerosis-associated genes were particularly enriched in endothelial cell and Mφ, and intercellular communication between endothelial cell and immune cells was predicted to increase in atherosclerosis. The interaction between ICAM1 / VCAM1 (EC1) and ITGB2 (immune cells, especially inflammatory Mφ) was speculated to be essential for the pathogenesis of atherosclerosis. Conclusions: We created a cell atlas of human nondiseased cardiac arteries, and characterized the cellular compositions in different cardiac arteries. Our results could be used as a reference to identify vascular disease-associated cell populations and help investigate new therapeutic strategies for vascular diseases.

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