Atherosclerosis results from lipid plaque buildup and chronic inflammation in the arteries. Plaques can rupture, causing heart attacks or strokes. While single-cell transcriptomics (scRNA-seq) has advanced research, the immune and structural cell mechanisms driving plaque progression remain incompletely understood, and existing datasets often lack comprehensive coverage and consistent annotations.
A Comprehensive Map of Plaque Cells
To address these gaps, a team led by Dr. Matthias Heinig (Helmholtz Munich and Technical University of Munich) and Dr. Peter Kastner (Roche Diagnostics) has created the most comprehensive single-cell atlas of human atherosclerotic plaques to date. The resource integrates data from around 250,000 high-quality annotated cells, with cell type classifications validated through expert consensus and confirmed by surface protein measurements, providing a robust reference for future research.
“By integrating diverse datasets into a unified atlas, we were able to resolve immune and vascular cell populations at an unprecedented level of detail. This allowed us to identify previously unrecognized cell states that play critical roles in plaque progression,” says Korbinian Träuble, first author of the study.
The integrated atlas offers several new insights into plaque biology. It defines distinct markers for plaque neutrophils, identifies a pro-angiogenic endothelial cell cluster enriched in advanced lesions, and describes specialized macrophage subsets. In addition, the study confirms that fibromyocytes are exclusive to vascular tissue. Together, these findings contribute to a deeper understanding of the immune and vascular cell diversity underlying plaque development and progression.
Enabling Reproducible and Translational Research
Beyond its biological contributions, the atlas offers a practical tool for the research community. It enables accurate automatic annotation of new datasets, improves experimental design by guiding sample size and detection power, and facilitates the deconvolution of bulk RNA-seq data. These applications improve the reproducibility and interpretability of large-scale studies.
“With this atlas, we provide the cardiovascular research community with a powerful resource to understand and target the cellular and molecular drivers of atherosclerosis,” says corresponding author Matthias Heinig.
“Our integrated atlas is not only a valuable resource for the scientific community, but also a tool that can accelerate translational research. It enables better experimental design and supports the development of more precise diagnostic and therapeutic strategies,” adds Peter Kastner, senior co-author.
To ensure broad availability, the team has made the atlas accessible through an interactive online platform. This resource is expected to accelerate research in cardiovascular biology and facilitate the translation of scientific findings into improved diagnostics and therapeutic strategies for cardiovascular disease, the world’s leading cause of death.
Original Publication
Traeuble et al., 2025: Integrated single-cell atlas of human atherosclerotic plaques. Nature Communications. DOI: 10.1038/s41467-025-63202-x
