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Single-Cell Sequencing of Mouse Heart Immune Infiltrate in Pressure Overload–Driven Heart Failure Reveals Extent of Immune Activation
Open accessAbstract
BACKGROUND: Inflammation is a key component of cardiac disease, with macrophages and T lymphocytes mediating essential roles in the progression to heart failure. Nonetheless, little insight exists on other immune subsets involved in the cardiotoxic response. METHODS: cells, we obtained a higher resolution identification of the immune cell subsets in the heart, at early and late stages of disease and in controls. We then integrated our findings using multiparameter flow cytometry, immunohistochemistry, and tissue clarification immunofluorescence in mouse and human. RESULTS: We found that most major immune cell subpopulations, including macrophages, B cells, T cells and regulatory T cells, dendritic cells, Natural Killer cells, neutrophils, and mast cells are present in both healthy and diseased hearts. Most cell subsets are found within the myocardium, whereas mast cells are found also in the epicardium. Upon induction of pressure overload, immune activation occurs across the entire range of immune cell types. Activation led to upregulation of key subset-specific molecules, such as oncostatin M in proinflammatory macrophages and PD-1 in regulatory T cells, that may help explain clinical findings such as the refractivity of patients with heart failure to anti-tumor necrosis factor therapy and cardiac toxicity during anti-PD-1 cancer immunotherapy, respectively. CONCLUSIONS: Despite the absence of infectious agents or an autoimmune trigger, induction of disease leads to immune activation that involves far more cell types than previously thought, including neutrophils, B cells, Natural Killer cells, and mast cells. This opens up the field of cardioimmunology to further investigation by using toolkits that have already been developed to study the aforementioned immune subsets. The subset-specific molecules that mediate their activation may thus become useful targets for the diagnostics or therapy of heart failure.
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Rockman, H. A., Ross, R. S., Harris, A. N., Knowlton, K. U., Steinhelper, M. E., Field, L. J., Ross, J., & Chien, K. R. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.18.8277 · Cited by 807
RetractedIntegrating single-cell transcriptomic data across different conditions, technologies, and species
Butler, A., Hoffman, P., Smibert, P., Papalexi, E., & Satija, R. (2018) · Nature Biotechnology · doi:10.1038/nbt.4096 · Cited by 13,174
Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
Ridker, P. M., Everett, B. M., Thuren, T., MacFadyen, J. G., Chang, W. H., Ballantyne, C., Fonseca, F., Nicolau, J., Koenig, W., Anker, S. D., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1707914 · Cited by 9,482
Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris
The Tabula Muris Consortium, coordination, O., coordination, L., processing, O. C. A., sequencing, L. P. A., analysis, C. D., annotation, C. T., Writing group, Supplemental text writing group, & Principal investigators (2018) · Nature · doi:10.1038/s41586-018-0590-4 · Cited by 2,842
Fulminant Myocarditis with Combination Immune Checkpoint Blockade
Johnson, D. B., Balko, J. M., Compton, M. L., Chalkias, S., Gorham, J., Xu, Y., Hicks, M., Puzanov, I., Alexander, M. R., Bloomer, T. L., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1609214 · Cited by 2,308
PD-L1 regulates the development, maintenance, and function of induced regulatory T cells
Francisco, L. M., Salinas, V. H., Brown, K. E., Vanguri, V. K., Freeman, G. J., Kuchroo, V. K., & Sharpe, A. H. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20090847 · Cited by 2,072
Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment
Azizi, E., Carr, A. J., Plitas, G., Cornish, A. E., Konopacki, C., Prabhakaran, S., Nainys, J., Wu, K., Kiseliovas, V., Setty, M., et al. (2018) · Cell · doi:10.1016/j.cell.2018.05.060 · Cited by 1,976
Epelman, S., Lavine, K. J., Beaudin, A. E., Sojka, D. K., Carrero, J. A., Calderon, B., Brija, T., Gautier, E. L., Ivanov, S., Satpathy, A. T., et al. (2014) · Immunity · doi:10.1016/j.immuni.2013.11.019 · Cited by 1,494
Self-Renewing Resident Cardiac Macrophages Limit Adverse Remodeling Following Myocardial Infarction
Dick, S. A., Macklin, J. A., Nejat, S., Momen, A., Clemente-Casares, X., Althagafi, M. G., Chen, J., Kantores, C., Hosseinzadeh, S., Aronoff, L., et al. (2019) · Nature Immunology · doi:10.1038/s41590-018-0272-2 · Cited by 883
Oxford IBD Cohort Investigators, West, N. R., Hegazy, A. N., Owens, B. M. J., Bullers, S. J., Linggi, B. E., Buonocore, S. M., Coccia, M., Görtz, D., This, S., et al. (2017) · Nature Medicine · doi:10.1038/nm.4307 · Cited by 812
Flagged first, then by citations
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Sorted by citations
Items 301–343 of 343
Cao, B., Zhao, Z., Cui, L., Li, J., Su, J., & Chen, X. (2026) · Journal of Visualized Experiments · doi:10.3791/69756 · Cited by 1
Yakhshimurodov, U. R., Yamashita, K., Kawamura, T., Miki, K., Taguchi, T., Saito, S., Abugessaisa, I., & Miyagawa, S. (2026) · Regenerative Therapy · doi:10.1016/j.reth.2026.101061 · Cited by 1
He, L., Zhang, D., Zhang, S., Ren, Z., Huangfu, Y., Cheng, X., & Song, Z. (2026) · PLoS ONE · doi:10.1371/journal.pone.0343296 · Cited by 1
Macrophage STING activation induces cardiomyocyte hypertrophy
Du, Y., Han, Y., Shi, Y., Xie, H., Qiu, X., Qi, Y., He, L., Wang, L., Kang, L., & Xu, B. (2026) · The Journal of Cardiovascular Aging · doi:10.20517/jca.2025.39 · Cited by 1
Wu, M., Sun, Y., Zhang, Y., Yang, Y.-C., He, Z.-X., Zhou, S., Wang, X., Xiao, H., Yu, M., Miao, C., et al. (2026) · Circulation · doi:10.1161/circulationaha.125.074024 · Cited by 1
A Recovery-Focused Framework for the Management of Cardiogenic Shock
Kyriakopoulos, C. P., Taleb, I., Hamouche, R., Tseliou, E., & Drakos, S. G. (2026) · Circulation Heart Failure · doi:10.1161/circheartfailure.126.014307 · Cited by 1
Patterns of immunological reactions in the pathogenesis of chronic heart failure: review
Андреевна, К. Е., Fediunina, V. A., & Анатольевна, Г. А. (2021) · Kardiologiia · doi:10.18087/cardio.2021.12.n1598 · Cited by 1
Single-Cell mRNA Sequencing in Precision Medicine: Promise and Challenges
Zhang, K. K., Li, J., Jeon, M. S., & Ramos, K. S. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-824010-6.00028-9 · Cited by 1
Single-Cell Sequencing of the Cardiovascular System: Challenges in Translation
Li, Z., & Zhou, B. (2021) · Cardiology Discovery · doi:10.1097/cd9.0000000000000027 · Cited by 1
Circadian rhythms and cardiac physiology: An essential interplay
Caputo, R., Idini, A., & Greco, C. M. (2024) · International review of cytology · doi:10.1016/bs.ircmb.2024.07.001 · Cited by 1
Panico, C., Kallikourdis, M., & Condorelli, G. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvaa156 · Cited by 1
Self-citationSplenic CD23+ B Cells: Preventing Adverse Remodeling by Limiting IgE Production
Smolgovsky, S. A., & Alcaide, P. (2025) · Circulation Research · doi:10.1161/circresaha.125.326725 · Cited by 1
Inflammatory biomarkers in ischemic heart disease
Groot, H. E. (2021) · University of Groningen research database (University of Groningen / Centre for Information Technology) · doi:10.33612/diss.156111034
Li, S., Ge, T., Xu, X., Xie, L., Song, S., Li, R., Li, H., & Tong, J. (2023) · Figshare · doi:10.6084/m9.figshare.24580293
Yang, Y., Liu, C., Wu, B., Ning, K., Gao, X., Zhang, J., Ding, X., Qin, Z., Bian, S., & huang, L. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4792353
Yu, Y., Yuan, H., Liu, W., Xue, Y., Liu, X., Hou, W., & Li, Y. (2024) · medRxiv · doi:10.1101/2024.04.26.24306471
Beslika, E. (2024) · doi:10.26481/dis.20240514eb
Huang, S., Yu-ling, W., Chen, M., Shen, J., Zhu, J., & Yu, H. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2024.113994
Deciphering immune cell heterogeneity in vascular diseases: Insights from single-cell sequencing
Zeng, W., Zhang, Y., Zhong, W., Chen, L., Gao, Y., Li, C., Zhao, Y., Shen, C., Zhao, R., Shi, B., et al. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.114719
Cardiac Macrophage: Insights from Murine Models and Translational Potential for Human Studies
Liu, Y., Wang, T. T., Lu, Y., Riaz, M., & Qyang, Y. (2024) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2025.05.001 · Cited by 1
Zhu, Y., Cao, B., Huang, K., & Liu, J. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.152063
Doelling, B., Chaudhari, M., Hoetker, D., Brittian, K. R., Nong, Y., Stephan, J., Jouja, I., Janis, H. I., Mitchell, T. C., Wysoczynski, M., et al. (2026) · Journal of the American Heart Association · doi:10.1161/jaha.125.047630
Integrated bioinformatic and in vivo analysis confirms the cardioprotective role of OPA1
Fong-McMaster, C., Pulente, S. M., Kennedy, L. S., Smith, T. K. T., Myers, S., Kanaan, M. N., Karam, C. Y., Cope, M., Levesque, M. M., McIlroy, E., et al. (2025) · BMC Cardiovascular Disorders · doi:10.1186/s12872-025-05413-0 · Cited by 1
Du, L., Sun, X., Gong, H., Wang, T., Jiang, L., Huang, C., Xu, X., Li, Z., Xu, H., Ma, L., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22613107
Additional file 1 of Identification and characterization of neutrophil heterogeneity in sepsis
Qi, X., Yu, Y., Sun, R., Huang, J., Liu, L., Yang, Y., Rui, T., & Sun, B. (2021) · Figshare · doi:10.6084/m9.figshare.13727645
Li, S., Ge, T., Xu, X., Xie, L., Song, S., Li, R., Li, H., & Tong, J. (2024) · Figshare · doi:10.6084/m9.figshare.24580437
Yuan, Y., Niu, Y., Ye, J., Yuejuan, X., He, X., & Chen, S. (2024) · Figshare · doi:10.6084/m9.figshare.25223416
Moazzami, K., Wang, M., Rahbar, A., Pearce, B. D., Shah, A. J., Sun, Y. V., Ko, Y.-A., Raggi, P., Bremner, J. D., Vaccarino, V., et al. (2026) · Psychosomatic Medicine · doi:10.1097/psy.0000000000001464
Koch, V., Ochs, A., Martin, S. S., Vogl, T. J., Ochs, M. M., Leistner, D. L. D. M., & Haberkorn, S. M. (2026) · NMR in Biomedicine · doi:10.1002/nbm.70288
Xu, K., Ma, L., Du, H., Huang, H., & Xu, Y. (2026) · Medicine · doi:10.1097/md.0000000000048404
Spatial imprints of emergent cardiomyocyte states in the pressure-overloaded heartPreprint
Liu, Y., Coles, A. M., Castiglione, J., Thiyagarajan, V. V., Clifton, K., Goyal, D., Wu, J., Sheridan, A., Vujić, A., Harris, K. M., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.04.721738
Liu, K.-Y., Chen, Y., Luo, Y., Zhang, L.-Q., & Chen, W.-L. (2026) · Acta Pharmacologica Sinica · doi:10.1038/s41401-026-01841-6
Liu, Z., Kwaku, O. E., Cui, Y., Xiong, L., Li, S. X., Zeng, L., Du, L., Wang, K., Zheng, J., Luo, D., et al. (2026) · Medicine · doi:10.1097/md.0000000000049074
Necroptosis is a key contributor to impaired cardiac repair following myocardial infarction
Rimon, R. A., Li, Y., Meganathan, I., Wang, F., Murray, A. G., Oudit, G. Y., Epelman, S., Clemente‐Casares, X., & Kassiri, Z. (2026) · Cell Death and Disease · doi:10.1038/s41419-026-08979-5
Fibroblast S1PR2 Amplifies NLRP3 Inflammasome Activation Under Pressure Overload
Zhou, C., Liu, Z., Wang, Z., Cui, Z., Wang, Q., Fang, X., Chen, X., Liu, J., Zhang, Y., Cao, H., et al. (2026) · Hypertension · doi:10.1161/hypertensionaha.126.27475
Seo, M., Kim, Y.-A., Kim, R., Lee, H. G., & Kim, M. S. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1814166
Bai, Z., Zhou, M., Qu, P., Shi, J., Gu, Y., Zhao, D., Lyu, J., Cheng, P., & Lei, Q. (2026) · Vessel Plus · doi:10.20517/2574-1209.2026.38
Wang, X., 徐洋, Pei, C., Zheng, H., & Cai, H. (2026) · Biomedicines · doi:10.3390/biomedicines14102278
Liu, Y., Li, J., Xiao, G., & He, C. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1946787
Panico, C., Felicetta, A., Kunderfranco, P., Cremonesi, M., Salvarani, N., Carullo, P., Colombo, F., Idini, A., Passaretti, M., Doro, R., et al. (2024) · Zenodo (CERN European Organization for Nuclear Research) · doi:10.5281/zenodo.10533107
Self-citation
Metadata
- Authors
- Martini, E., Kunderfranco, P., Peano, C., Carullo, P., Cremonesi, M., Schorn, T., Carriero, R., Termanini, A., Colombo, F. S., Jachetti, E., Panico, C., Faggian, G., Fumero, A., Torracca, L., Molgora, M., Cibella, J., Pagiatakis, C., Brummelman, J., Alvisi, G., Mazza, E. M. C., Colombo, M. P., Lugli, E., Condorelli, G., & Kallikourdis, M.
- Affiliations
- IRCCS Humanitas Research Hospital (IT)
- Institute of Genetic and Biomedical Research (IT)
- Humanitas University (IT)
- Fondazione IRCCS Istituto Nazionale dei Tumori (IT)
- University of Verona (IT)
- Cardiac Surgery Division, Department of Cardiovascular Medicine (A.F., L.T.), Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
- Fondazione Humanitas per la Ricerca (IT)
- Corresponding author
- Martini, Elisa
- Kunderfranco, Paolo
- ORCID
- Martini, Elisa
- Kunderfranco, Paolo
- Peano, Clelia
- Carullo, Pierluigi
- Cremonesi, Marco
- Schorn, Tilo
- Carriero, Roberta
- Termanini, Alberto
- Colombo, Federico Simone
- Jachetti, Elena
- Panico, Cristina
- Faggian, Giuseppe
- Torracca, Lucia
- Molgora, Martina
- Cibella, Javier
- Pagiatakis, Christina
- Brummelman, Jolanda
- Alvisi, Giorgia
- Mazza, Emilia Maria Cristina
- Colombo, Mario Paolo
- Lugli, Enrico
- Condorelli, Gianluigi
- Kallikourdis, Marinos
- Venue
- Circulation
- Published
- 2019-12-17
- Volume
- 140
- Issue
- 25
- Pages
- 2089-2107
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2982367920
- Cited by
- 341
- References
- 52
- Citations by year
- 2026: 31 · 2025: 56 · 2024: 58 · 2023: 57 · 2022: 57 · 2021: 50 · 2020: 31 · 2019: 1
- FWCI
- 25.11
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- cc-by
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- IrInSubria (University of Insubria) (submittedVersion, cc-by)
- Radboud Repository (Radboud University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Keywords
- heart failure, pressure overload, cardiac inflammation, macrophages, T cells, regulatory T cells, mast cells, neutrophils, natural killer cells, dendritic cells, B cells, oncostatin M, PD-1, epicardium
- MeSH terms
- Animals, B-Lymphocytes, Dendritic Cells, Flow Cytometry, Heart Failure, Humans, Immunity, Cellular, Killer Cells, Natural, Mice, Inbred C57BL, Myocardium, Neutrophils, Sequence Analysis, RNA, Mice, Single-Cell Analysis
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