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Review

Immunothrombotic Cell–Cell Communication Networks in Coronary Atherosclerosis: Critical Insights from Single-Cell and Spatial Systems Biology

by
Beata Krasińska
1,
Antoni Staniewski
2,
Oliwia Kalus
2,
Joanna Maćkowiak
2,
Zofia Szymańska
2,
Zofia Gramala
2,
Katarzyna Zalewska
2,
Michał Karpiński
2,
Paulina Mertowska
3,
Łucja Rolek
3,4,
Kinga Koziarska
5,
Krzysztof J. Filipiak
6,
Mansur Rahnama
7,
Mariusz Kowalewski
8,
Calogera Pisano
9,10,
Giuseppe Maria Raffa
9,10,
Zbigniew Krasiński
11,
Piotr Suwalski
8,
Vincenzo Nuzzi
12,
Ewelina Grywalska
3 and
Tomasz Urbanowicz
13,*add Show full author list remove Hide full author list
1
Department of Hypertensiology, Angiology, and Internal Medicine, Poznan University of Medical Sciences, 61-848 Poznan, Poland
2
Student Research Group of Cardiology, Poznan University of Medical Sciences, 61-701 Poznan, Poland
3
Department of Experimental Immunology, Faculty of Medical Sciences, Medical University of Lublin, 20-093 Lublin, Poland
4
Student Research Group of Experimental Immunology, Medical University of Lublin, 20-093 Lublin, Poland
5
Central University Hospital, Poznan University of Medical Sciences, 60-352 Poznan, Poland
6
The Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland
7
Department of Dental Surgery, Medical University of Lublin, 20-093 Lublin, Poland
8
Department of Cardiac Surgery, Center of Postgraduate Medical Education, Central Clinical Hospital of the Ministry of Interior, 02-507 Warszawa, Poland
9
Department of Research, IRCCS ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), 90127 Palermo, Italy
10
Department of Precision Medicine in Medical Surgical and Critical Area (Me.Pre.C.C.), University of Palermo, 90134 Palermo, Italy
11
Department of Vascular, Endovascular Surgery, Angiology and Phlebology, Poznan University of Medical Science, 61-848 Poznan, Poland
12
Department of Clinical Cardiology and Heart Failure, IRCCS ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies), 90127 Palermo, Italy
13
Cardiac Surgery and Transplantology Department, Poznan University of Medical Sciences, 61-848 Poznan, Poland
 
add Show full affiliation list
 
remove Hide full affiliation list
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2026, 27(13), 5900; https://doi.org/10.3390/ijms27135900
Submission received: 16 May 2026 / Revised: 19 June 2026 / Accepted: 24 June 2026 / Published: 30 June 2026
(This article belongs to the Special Issue Molecular Pathophysiology and Treatment of Coronary Artery Disease)
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Abstract

Coronary artery disease (CAD) is increasingly recognized as a thromboinflammatory disorder in which innate immune activation and coagulation are tightly coupled within the plaque microenvironment. Emerging single-cell and spatial technologies have refined this paradigm by demonstrating that these processes are not diffusely distributed but instead concentrated within discrete cellular niches. This narrative review critically evaluates mechanistic and translational studies integrating single-cell RNA sequencing, spatial transcriptomics, and ligand–receptor modeling to characterize cell–cell communication networks driving immunothrombosis in CAD. Converging evidence from single-cell and spatial studies indicates substantial heterogeneity among macrophages, neutrophils, and smooth muscle cells, with functionally distinct subpopulations contributing differentially to inflammation, matrix remodeling, and thrombogenicity. Spatial analyses further demonstrate that procoagulant and inflammatory programs converge in anatomically defined high-risk regions, particularly at the plaque shoulder and sites of endothelial dysfunction. However, whether these transcriptional states represent causal drivers or epiphenomena remains unresolved. Many insights are derived from murine models or dissociated tissues, raising concerns regarding translational relevance and loss of spatial context. Additionally, computational inference of intercellular communication remains indirect and requires functional validation. In conclusion, immunothrombosis in CAD should be interpreted as an emergent property of spatially organized cellular networks rather than a uniform inflammatory state. While these approaches identify candidate therapeutic nodes, their clinical translation and the central challenge is to distinguish causal regulatory nodes from transcriptional correlates generated by high-dimensional profiling.
Keywords: coronary artery disease; atherosclerosis; thrombosis; inflammation; single-cell analysis; transcriptome mapping coronary artery disease; atherosclerosis; thrombosis; inflammation; single-cell analysis; transcriptome mapping

Share and Cite

MDPI and ACS Style

Krasińska, B.; Staniewski, A.; Kalus, O.; Maćkowiak, J.; Szymańska, Z.; Gramala, Z.; Zalewska, K.; Karpiński, M.; Mertowska, P.; Rolek, Ł.; et al. Immunothrombotic Cell–Cell Communication Networks in Coronary Atherosclerosis: Critical Insights from Single-Cell and Spatial Systems Biology. Int. J. Mol. Sci. 2026, 27, 5900. https://doi.org/10.3390/ijms27135900

AMA Style

Krasińska B, Staniewski A, Kalus O, Maćkowiak J, Szymańska Z, Gramala Z, Zalewska K, Karpiński M, Mertowska P, Rolek Ł, et al. Immunothrombotic Cell–Cell Communication Networks in Coronary Atherosclerosis: Critical Insights from Single-Cell and Spatial Systems Biology. International Journal of Molecular Sciences. 2026; 27(13):5900. https://doi.org/10.3390/ijms27135900

Chicago/Turabian Style

Krasińska, Beata, Antoni Staniewski, Oliwia Kalus, Joanna Maćkowiak, Zofia Szymańska, Zofia Gramala, Katarzyna Zalewska, Michał Karpiński, Paulina Mertowska, Łucja Rolek, and et al. 2026. "Immunothrombotic Cell–Cell Communication Networks in Coronary Atherosclerosis: Critical Insights from Single-Cell and Spatial Systems Biology" International Journal of Molecular Sciences 27, no. 13: 5900. https://doi.org/10.3390/ijms27135900

APA Style

Krasińska, B., Staniewski, A., Kalus, O., Maćkowiak, J., Szymańska, Z., Gramala, Z., Zalewska, K., Karpiński, M., Mertowska, P., Rolek, Ł., Koziarska, K., Filipiak, K. J., Rahnama, M., Kowalewski, M., Pisano, C., Raffa, G. M., Krasiński, Z., Suwalski, P., Nuzzi, V., ... Urbanowicz, T. (2026). Immunothrombotic Cell–Cell Communication Networks in Coronary Atherosclerosis: Critical Insights from Single-Cell and Spatial Systems Biology. International Journal of Molecular Sciences, 27(13), 5900. https://doi.org/10.3390/ijms27135900

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