Atherosclerotic plaques in the carotid arteries are a common cause of strokes. Why some plaques remain stable while others suddenly rupture is still not fully understood. An international research group, with significant involvement from the German Centre for Cardiovascular Research (DZHK), has now investigated the cellular and molecular architecture of such plaques with high spatial resolution.
The study, published in Nature Communications, was led by Jessica Pauli and Lars Maegdefessel. Both conduct research at the Technical University of Munich and are members of the DZHK. The study published in Nature Communications combines bulk and single-cell RNA sequencing with spatial transcriptomics. Early and advanced lesions from the same carotid artery of patients after carotid endarterectomy were analysed. This study design allows particularly reliable statements to be made about plaque development.
Different plaque types with characteristic cell distribution
The results show that atherosclerotic plaques are not uniform structures. Instead, they can be classified into different types based on their morphology and cellular composition. The decisive factor here is not only which cell types are present, but also where they are located within the plaque.
The spatial organisation of different macrophage states became particularly clear. These immune cells arrange themselves in characteristic zones, for example near the vessel lumen, in the fibrous cap or in the necrotic core. The findings suggest functional differences and local transitions between inflammatory and lipid-processing macrophages in areas relevant to plaque instability.
Furthermore, new states of vascular muscle cells were described and a close spatial proximity of macrophages and endothelial cells in particular in deeper plaque zones was demonstrated.
Significance for prevention and translational research at the DZHK
In addition to cell architecture, the study also took clinical risk factors into account. It showed that smoking is associated with specific changes in gene activity and cell distribution within the plaques, suggesting direct effects on the vessel wall.
The study provides a detailed reference image of the cellular microenvironment of human plaques. These findings form an important basis for the development of new markers for identifying unstable plaques and for targeted preventive and therapeutic approaches. The study thus makes a key contribution to the DZHK's translational cardiovascular research with the aim of better predicting and preventing strokes and heart attacks in the future.
Original publication:
Pauli J et al. Single cell spatial transcriptomics integration deciphers the morphological heterogeneity of atherosclerotic carotid arteries. Nature Communications, 2025
