Pro-Fibrotic Macrophage Subtypes: SPP1+ Macrophages as a Key Player and Therapeutic Target in Cardiac Fibrosis?
Open accessAbstract
Cardiac fibrosis is a major driver of heart failure, a leading cause of morbidity and mortality worldwide. Advances in single-cell transcriptomics have revealed the pivotal role of SPP1+ macrophages in the pathogenesis of cardiac fibrosis, positioning them as critical mediators and promising therapeutic targets. SPP1+ macrophages, characterized by elevated expression of secreted phosphoprotein 1 (SPP1) and often co-expressing Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), localize to fibrotic niches in the heart and other organs. These cells interact with activated fibroblasts and myofibroblasts, driving extracellular matrix remodeling and fibrosis progression. Their differentiation is orchestrated by signals such as CXCL4, GM-CSF, and IL-17A, further emphasizing their regulatory complexity. Therapeutic strategies targeting SPP1+ macrophages have shown encouraging preclinical results. Approaches include silencing Spp1 using antibody–siRNA conjugates and modulating key pathways involved in macrophage differentiation. These interventions have effectively reduced fibrosis and improved cardiac function in animal models. The mechanisms underlying SPP1+ macrophage function in cardiac fibrosis provide a foundation for innovative therapies aimed at mitigating pathological remodeling and improving outcomes in patients with heart failure. This emerging field has significant potential to transform the treatment of fibrotic heart disease.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Myocarditis is not only a transient inflammatory condition but a highly orchestrated process involving temporally regulated immune-stromal interactions that critically determine disease outcome.
“Our findings support and extend previous observations that myocarditis is not only a transient inflammatory condition but a highly orchestrated process involving temporally regulated immune–stromal interactions that critically determine the outcome of the disease [9,30].”
From Cardiac Macrophages Exhibit Dynamic Heterogeneity and Functional Specialization During Experimental Autoimmune Myocarditis. (2026) · cites this paper as [30]
The Introduction (section 1; page unavailable) describes macrophages influencing fibrogenesis through mesenchymal cells and links maladaptive fibrosis to organ failure. Section 4 also describes inflammatory and reparative macrophage activity after injury. These passages support a role for immune–stromal interactions in cardiac outcomes, but they do not establish the claim specifically for myocarditis or describe temporally regulated interactions determining its outcome. (LLM, conf=0.82)
Experimental — accuracy not yet measuredSPP1-expressing macrophages have emerged as a conserved pro-fibrotic population across human inflammatory cardiomyopathies.
“while SPP1-expressing macrophages have emerged as a conserved pro-fibrotic population across human inflammatory cardiomyopathies [30].”
From Cardiac Macrophages Exhibit Dynamic Heterogeneity and Functional Specialization During Experimental Autoimmune Myocarditis. (2026) · cites this paper as [30]
Section 4 reports that SPP1+ macrophages expand in human heart tissue after myocardial infarction and are associated with fibrotic remodeling. The Conclusions describe their relevance across organs as suggesting a conserved fibrosis mechanism. Neither passage establishes that they are a conserved population across human inflammatory cardiomyopathies; the human cardiac example is post-infarction tissue. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe coexistence of pro-inflammatory (Mac-rMHCII, Mono-C) and potentially reparative (Mac-ResL, Mac-TLF) macrophage subsets suggests that broad immunosuppression may unintentionally impair resolution processes.
“The coexistence of pro-inflammatory (Mac-rMHCII, Mono-C) and potentially reparative (Mac-ResL, Mac-TLF) macrophage subsets suggests that broad immunosuppression may unintentionally impair resolution processes [9,10,30].”
From Cardiac Macrophages Exhibit Dynamic Heterogeneity and Functional Specialization During Experimental Autoimmune Myocarditis. (2026) · cites this paper as [30]
Section 4 describes macrophages with inflammatory and reparative functions and says that some subtypes express genes associated with both. It does not identify the four named subsets or say that broad immunosuppression may impair resolution; Section 8 instead discusses targeting distinct macrophage populations to mitigate fibrosis. The page numbers are unavailable in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Mechanisms of fibrosis: therapeutic translation for fibrotic disease
Wynn, T. A., & Ramalingam, T. R. (2012) · Nature Medicine · doi:10.1038/nm.2807 · Cited by 3,541 · see citing works
Global burden of heart failure: a comprehensive and updated review of epidemiology
Savarese, G., Becher, P. M., Lund, L. H., Seferovic, P. M., Rosano, G. M. C., & Coats, A. J. S. (2022) · Cardiovascular Research · doi:10.1093/cvr/cvac013 · Cited by 3,482 · see citing works
Fadok, V. A., Bratton, D. L., Konowal, A., Freed, P. W., Westcott, J. Y., & Henson, P. M. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1112 · Cited by 3,166 · see citing works
Fibrosis: from mechanisms to medicines
Henderson, N. C., Rieder, F., & Wynn, T. A. (2020) · Nature · doi:10.1038/s41586-020-2938-9 · Cited by 1,868 · see citing works
Resolving the fibrotic niche of human liver cirrhosis at single-cell level
Ramachandran, P., Dobie, R., Wilson-Kanamori, J. R., Dora, E. F., Henderson, B. E. P., Luu, N. T., Portman, J. R., Matchett, K. P., Brice, M., Marwick, J. A., et al. (2019) · Nature · doi:10.1038/s41586-019-1631-3 · Cited by 1,784 · see citing works
Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair
Duffield, J. S., Forbes, S. J., Constandinou, C. M., Clay, S., Partolina, M., Vuthoori, S., Wu, S., Lang, R., & Iredale, J. P. (2005) · Journal of Clinical Investigation · doi:10.1172/jci200522675 · Cited by 1,649 · see citing works
Trends in Heart Failure Incidence and Survival in a Community-Based Population
Roger, V. L. (2004) · JAMA · doi:10.1001/jama.292.3.344 · Cited by 1,591 · see citing works
Lipid-associated macrophages control metabolic homeostasis in a Trem2-dependent manner
Jaitin, D. A., Adlung, L., Thaiss, C. A., Weiner, A., Li, B., Descamps, H., Lundgren, P., Bleriot, C., Liu, Z., Deczkowska, A., et al. (2019) · Cell · doi:10.1016/j.cell.2019.05.054 · Cited by 1,377 · see citing works
Frangogiannis, N. G. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvaa324 · Cited by 1,229 · see citing works
Gulati, A., Jabbour, A., Ismail, T. F., Guha, K., Khwaja, J., Raza, S., Morarji, K., Brown, T. D. H., Ismail, N. A., Dweck, M. R., et al. (2013) · JAMA · doi:10.1001/jama.2013.1363 · Cited by 1,183 · see citing works
Assessment of Myocardial Fibrosis With Cardiovascular Magnetic Resonance
Mewton, N., Liu, C. Y., Croisille, P., Bluemke, D. A., & Lima, J. A. C. (2011) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2010.11.013 · Cited by 987 · see citing works
Qi, J., Sun, H., Zhang, Y., Wang, Z., Xun, Z., Li, Z., Ding, X., Bao, R., Hong, L., Jia, W., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29366-6 · Cited by 983 · see citing works
The Phagocytic Function of Macrophage-Enforcing Innate Immunity and Tissue Homeostasis
Hirayama, D., Iida, T., & Nakase, H. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms19010092 · Cited by 927 · see citing works
Genetic lineage tracing defines myofibroblast origin and function in the injured heart
Kanisicak, O., Khalil, H., Ivey, M. J., Karch, J. M., Maliken, B. D., Correll, R. N., Brody, M. J., Lin, S. J., Aronow, B. J., Tallquist, M. D., et al. (2016) · Nature Communications · doi:10.1038/ncomms12260 · Cited by 896 · see citing works
Cardioimmunology: the immune system in cardiac homeostasis and disease
Świrski, F. K., & Nahrendorf, M. (2018) · Nature reviews. Immunology · doi:10.1038/s41577-018-0065-8 · Cited by 853 · see citing works
Lin, S., Kisseleva, T., Brenner, D. A., & Duffield, J. S. (2008) · American Journal Of Pathology · doi:10.2353/ajpath.2008.080433 · Cited by 834 · see citing works
Proliferating SPP1/MERTK-expressing macrophages in idiopathic pulmonary fibrosis
Morse, C., Tabib, T., Sembrat, J., Buschur, K. L., Bittar, H. E. T., Valenzi, E., Jiang, Y., Kass, D. J., Gibson, K. F., Chen, W., et al. (2019) · European Respiratory Journal · doi:10.1183/13993003.02441-2018 · Cited by 832 · see citing works
Spatial multi-omic map of human myocardial infarction
Kuppe, C., Ramirez Flores, R. O., Li, Z., Hayat, S., Levinson, R. T., Liao, X., Hannani, M. T., Tanevski, J., Wünnemann, F., Nagai, J. S., et al. (2022) · Nature · doi:10.1038/s41586-022-05060-x · Cited by 772 · see citing works
Self-citationDecoding myofibroblast origins in human kidney fibrosis
Kuppe, C., Ibrahim, M. M., Kranz, J., Zhang, X., Ziegler, S., Perales-Patón, J., Jansen, J., Reimer, K. C., Smith, J. R., Dobie, R., et al. (2021) · Nature · doi:10.1038/s41586-020-2941-1 · Cited by 769 · see citing works
Cross-tissue single-cell landscape of human monocytes and macrophages in health and disease
Mulder, K., Patel, A. A., Kong, W. T., Piot, C., Halitzki, E., Dunsmore, G., Khalilnezhad, S., Irac, S. E., Dubuisson, A., Chevrier, M., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.07.007 · Cited by 678 · see citing works
Myocardial Interstitial Fibrosis in Heart Failure
González, A., Schelbert, E. B., Dı́ez, J., & Butler, J. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.02.021 · Cited by 668 · see citing works
Resident fibroblast lineages mediate pressure overload–induced cardiac fibrosis
Moore‐Morris, T., Guimarães‐Camboa, N., Banerjee, I., Zambon, A. C., Kisseleva, T., Velayoudon, A., Stallcup, W. B., Gu, Y., Dalton, N. D., Cedenilla, M., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci74783 · Cited by 622 · see citing works
Fallowfield, J. A., Mizuno, M., Kendall, T. J., Constandinou, C. M., Benyon, R. C., Duffield, J. S., & Iredale, J. P. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.8.5288 · Cited by 479 · see citing works
Anatomy of a Discovery: M1 and M2 Macrophages
Mills, C. D. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00212 · Cited by 449 · see citing works
The big five in fibrosis: Macrophages, myofibroblasts, matrix, mechanics, and miscommunication
Pakshir, P., & Hinz, B. (2018) · Matrix Biology · doi:10.1016/j.matbio.2018.01.019 · Cited by 396 · see citing works
From Systemic Inflammation to Myocardial Fibrosis
Paulus, W. J., & Zile, M. R. (2021) · Circulation Research · doi:10.1161/circresaha.121.318159 · Cited by 396 · see citing works
Macrophages in cardiovascular diseases: molecular mechanisms and therapeutic targets
Chen, R., Zhang, H., Tang, B., Luo, Y., Yang, Y., Zhong, X., Chen, S., Xu, X., Huang, S., & Liu, C. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01840-1 · Cited by 387 · see citing works
Severe lung fibrosis requires an invasive fibroblast phenotype regulated by hyaluronan and CD44
Li, Y., Jiang, D., Liang, J., Meltzer, E. B., Gray, A., Miura, R., Wogensen, L., Yamaguchi, Y., & Noble, P. W. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20102510 · Cited by 382 · see citing works
Silvin, A., Uderhardt, S., Piot, C., Da Mesquita, S., Yang, K., Geirsdottir, L., Mulder, K., Eyal, D., Liu, Z., Bridlance, C., et al. (2022) · Immunity · doi:10.1016/j.immuni.2022.07.004 · Cited by 368 · see citing works
Identification of a broadly fibrogenic macrophage subset induced by type 3 inflammation
Fabre, T., Barron, A. M. S., Christensen, S. M., Asano, S., Bound, K., Lech, M. P., Wadsworth, M. H., Chen, X., Wang, C., Wang, J., et al. (2023) · Science Immunology · doi:10.1126/sciimmunol.add8945 · Cited by 355 · see citing works
Hoeft, K., Schaefer, G. J. L., Kim, H., Schumacher, D., Bleckwehl, T., Long, Q., Klinkhammer, B. M., Peisker, F., Koch, L., Nagai, J. S., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112131 · Cited by 323 · see citing works
Self-citationThe fibrosis-cell death axis in heart failure
Piek, A., de Boer, R. A., & Silljé, H. H. W. (2016) · Heart Failure Reviews · doi:10.1007/s10741-016-9536-9 · Cited by 304 · see citing works
Anti‐inflammatory therapies in myocardial infarction: failures, hopes and challenges
Huang, S., & Frangogiannis, N. G. (2018) · British Journal of Pharmacology · doi:10.1111/bph.14155 · Cited by 279 · see citing works
Recruited macrophages elicit atrial fibrillation
Hulsmans, M., Schloss, M. J., Lee, I., Bapat, A. C., Iwamoto, Y., Vinegoni, C., Paccalet, A., Yamazoe, M., Grune, J., Pabel, S., et al. (2023) · Science · doi:10.1126/science.abq3061 · Cited by 229 · see citing works
Trem2 promotes foamy macrophage lipid uptake and survival in atherosclerosis
Patterson, M. T., Firulyova, M. M., Xu, Y., Hillman, H., Bishop, C., Zhu, A., Hickok, G. H., Schrank, P. R., Ronayne, C. E., Caillot, Z., et al. (2023) · Nature Cardiovascular Research · doi:10.1038/s44161-023-00354-3 · Cited by 190 · see citing works
Role of Osteopontin in Cardiac Fibrosis and Remodeling in Angiotensin II-Induced Cardiac Hypertrophy
Matsui, Y., Jia, N., Okamoto, H., Kon, S., Onozuka, H., Akino, M., Liu, L., Morimoto, J. O., Rittling, S. R., Denhardt, D. T., et al. (2004) · Hypertension · doi:10.1161/01.hyp.0000128621.68160.dd · Cited by 188 · see citing works
Renkl, A. C., Wussler, J., Ahrens, T., Thoma, K., Kon, S., Uede, T., Martin, S. F., Simon, J. C., & Weiss, J. M. (2005) · Blood · doi:10.1182/blood-2004-08-3228 · Cited by 173 · see citing works
Reduced postischemic macrophage infiltration and interstitial fibrosis in osteopontin knockout mice
Persy, V. P., Verhulst, A., Ysebaert, D., Greef, K. E. D., & Broe, M. E. D. (2003) · Kidney International · doi:10.1046/j.1523-1755.2003.00767.x · Cited by 161 · see citing works
Type 3 cytokines IL-17A and IL-22 drive TGF-β–dependent liver fibrosis
Fabre, T., Molina, M. F., Soucy, G., Goulet, J.-P., Willems, B., Villeneuve, J.-P., Bilodeau, M., & Shoukry, N. H. (2018) · Science Immunology · doi:10.1126/sciimmunol.aar7754 · Cited by 155 · see citing works
Coulis, G., Jaime, D., Guerrero-Juarez, C., Kastenschmidt, J. M., Farahat, P. K., Nguyen, Q., Pervolarakis, N., McLinden, K., Thurlow, L., Movahedi, S., et al. (2023) · Science Advances · doi:10.1126/sciadv.add9984 · Cited by 150 · see citing works
Kramer, C. M., Appelbaum, E. A., Desai, M. Y., Desvigne-Nickens, P. M., Dimarco, J., Friedrich, M. G., Geller, N. L., Dolman, S. F., Ho, C. Y., Jerosch‐Herold, M., et al. (2015) · American Heart Journal · doi:10.1016/j.ahj.2015.05.013 · Cited by 148 · see citing works
Therapeutic Targets in Heart Failure
Schelbert, E. B., Fonarow, G. C., Bonow, R. O., Butler, J., & Gheorghiade, M. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.01.068 · Cited by 142 · see citing works
Macrophage functions in wound healing
Kloc, M., Ghobrial, R. M., Wosik, J., Lewicka, A., Lewicki, S., & Kubiak, J. Z. (2018) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.2772 · Cited by 131 · see citing works
Cardiac Fibrosis in the Pressure Overloaded Left and Right Ventricle as a Therapeutic Target
Schimmel, K., Ichimura, K., Reddy, S., Haddad, F., & Spiekerkoetter, E. F. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.886553 · Cited by 100 · see citing works
Kramann, R., Machado, F. G., Wu, H., Kusaba, T., Hoeft, K., Schneider, R. K., & Humphreys, B. D. (2018) · JCI Insight · doi:10.1172/jci.insight.99561 · Cited by 94 · see citing works
Theofilatos, K., Stojković, S., Hasman, M., van der Laan, S. W., Baig, F., Barallobre‐Barreiro, J., Schmidt, L. E., Yin, S., Yin, X., Burnap, S. A., et al. (2023) · Circulation Research · doi:10.1161/circresaha.123.322590 · Cited by 90 · see citing works
Pathogenic Potential of Hic1-Expressing Cardiac Stromal Progenitors
Soliman, H., Paylor, B., Scott, R. W., Lemos, D. R., Chang, C., Arostegui, M., Low, M., Lee, C., Fiore, D., Braghetta, P., et al. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2019.12.008 · Cited by 86 · see citing works
Huang, K. Y., Mishra, K., Park, H., Yi, X., Ouyang, J. F., Petretto, E. G., & Behmoaras, J. V. (2023) · eLife · doi:10.7554/elife.85530 · Cited by 62 · see citing works
Osteopontin is a proximal effector of leptin-mediated non-alcoholic steatohepatitis (NASH) fibrosis
Coombes, J. D., Choi, S. S., Swiderska‐Syn, M., Manka, P. P., Reid, D. T., Palma, E., Briones-Orta, M. A., Xie, G., Younis, R. L., Kitamura, N., et al. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.10.028 · Cited by 59 · see citing works
Osteopontin delays resolution of liver fibrosis
Leung, T.-M., Wang, X., Kitamura, N., Fiel, M. I., & Nieto, N. (2013) · Laboratory Investigation · doi:10.1038/labinvest.2013.104 · Cited by 54 · see citing works
The roles of Th cells in myocardial infarction
Liu, J., Liu, F., Liang, T., Zhou, Y., Su, X., Li, X., Zeng, J., Qu, P., Wang, Y., Chen, F., et al. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-02064-6 · Cited by 45 · see citing works
Cardiac and skeletal myopathy in Fabry disease: a clinicopathologic correlative study
Chimenti, C., Padua, L., Pazzaglia, C., Morgante, E., Centurion, C., Antuzzi, D., Russo, M. A., & Frustaci, A. (2012) · Human Pathology · doi:10.1016/j.humpath.2011.09.020 · Cited by 42 · see citing works
Inhibition of PDIA3 in club cells attenuates osteopontin production and lung fibrosis
Kumar, A., Elko, E. A., Bruno, S. R., Mark, Z. F., Chamberlain, N., Korwin-Mihavics, B. R., Chandrasekaran, R., Walzer, J., Ruban, M., Gold, C., et al. (2021) · Thorax · doi:10.1136/thoraxjnl-2021-216882 · Cited by 40 · see citing works
Neutralizing antibody against osteopontin attenuates non-alcoholic steatohepatitis in mice
Honda, M., Kimura, C., Uede, T., & Kon, S. (2020) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-020-00554-7 · Cited by 34 · see citing works
Jiang, Y., Yu, W., Hu, T., Peng, H., Hu, F., Yuan, Y., Liu, X., Lai, S., Zhou, J., & Dong, X. S. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1335333 · Cited by 31 · see citing works
Midwall Fibrosis Is an Independent Predictor of Mortality in Patients With Aortic Stenosis
Dweck, M. R., Joshi, S., Murigu, T., Alpendurada, F., Jabbour, A., Melina, G., Banya, W., Gulati, A., Roussin, I., Raza, S., et al. (2011) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2011.03.064 · Cited by 23 · see citing works
Therapeutic Spp1 silencing in TREM2+ cardiac macrophages suppresses atrial fibrillation
Momin, N., Pabel, S., Rudra, A., Kumowski, N., Lee, I., Seung, H., Mentkowski, K. I., Bapat, A. C., Yamazoe, M., Stengel, L., et al. (2026) · Nature Cardiovascular Research · doi:10.1038/s44161-026-00806-6 · Cited by 23 · see citing works
Multiomic Spatial Mapping of Myocardial Infarction and Implications for Personalized Therapy
Schumacher, D., & Kramann, R. (2022) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.122.318333 · Cited by 22 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Kulzhanova, G., Klee, A., Botros, M., Hansen, V. L., Reuter, J. E., Tashbib, E. T., Fadial, E., Ricciardi, B. F., Giordano, B. D., & Wu, C. (2026) · Arthritis & Rheumatology · doi:10.1002/art.70033 · Cited by 7 · see citing works
Cardiac Macrophages across Space and Time: Roles in Homeostasis, Disease, and Remodeling
Shrestha, S., & Dick, S. A. (2026) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2026.02.025 · Cited by 7 · see citing works
Macrophages and fibroblasts in cardiac fibrosis: interactions and transformation
Kim, D., & Baek, J.-H. (2025) · Exploration of Immunology · doi:10.37349/ei.2025.1003211 · Cited by 4 · see citing works
Mesfin, J. M., Chen, A., Lyons, Q. P., Nguyen, M. B., Karkanitsa, M. L., Yu, J. D., Ninh, V. K., Gardner, E. E., Wong, E. G., Paleti, S. N., et al. (2025) · Advanced Healthcare Materials · doi:10.1002/adhm.202503469 · Cited by 4 · see citing works
Stoyell‐Conti, F. F., Kaiser, A. M., Rojas, M. G., Wei, Y., Sussman, M. S., López-McCormick, J. S., Tabbara, M., Yang, X., Vázquez-Padrón, R. I., & Martinez, L. (2025) · Cells · doi:10.3390/cells14241998 · Cited by 4 · see citing works
Ji, W., Wen, J., Tong, N., Guo, F., Zheng, J., Wen, X., Liu, J., (23771), N. Z., & Hou, B. (2026) · Acta Biomaterialia · doi:10.1016/j.actbio.2026.03.001 · Cited by 4 · see citing works
Zhu, Z., Xu, R., Han, J., Jia, H., Wang, Y., Weng, W., & Zhang, K. (2025) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2025.140429 · Cited by 3 · see citing works
Yu, M., & Fu, J. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1749098 · Cited by 3 · see citing works
Kozdrowicki, M., Szczepaniak, P., Kyslyi, V. F., Carnevale, L., Carnevale, D., Lembo, G., Guzik, T. J., & Mikolajczyk, T. P. (2026) · Cardiovascular Research · doi:10.1093/cvr/cvag054 · Cited by 4 · see citing works
Kuang, W., Cui, H., Li, Q., Duan, S., Liu, D., Liu, T., Wang, J., Li, W., Chen, Q., Li, J., et al. (2025) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2025.10.062 · Cited by 2 · see citing works
Liang, T., Zhou, B., Changwen, G. U., Peng, G., Ning, X., & Huang, M. N. (2026) · Journal of Orthopaedic Surgery and Research · doi:10.1186/s13018-025-06617-y · Cited by 1 · see citing works
Fibrosis as the Engine of Kidney Functional Decline
Koch, L., Dilmen, E., Jansen, J., & Kramann, R. (2026) · Journal of the American Society of Nephrology · doi:10.1681/asn.0000001154 · Cited by 1 · see citing works
Hemodynamics and matrix stiffness shape the pathogenicity of SPP1+ macrophages
Zhang, H., Han, J., Zhu, S., Yi, M., Fan, K., Chang, R., Shi, Y., & Dong, H. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1856522 · Cited by 1 · see citing works
Macrophage regulation of extracellular matrix remodeling in aging skeletal muscle
Cui, C., Nazario, J. C., Stephen, I. A., Baranzini, M., Zhang, Y., De, S., Sen, P., Ferrucci, L., & Gorospe, M. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103208 · Cited by 1 · see citing works
Spatial transcriptomics reveals layered immune-metabolic architecture of giant cell myocarditisPreprint
Musigk, N., Sudy, A., Suwalski, P., Jechow, K., Liebig, J., Bischoff, P., Just, I. A., Falk, V., Schoenrath, F., Eils, R., et al. (2025) · medRxiv · doi:10.64898/2025.12.15.25342188 · Cited by 1 · see citing works
Stefanska, M., Kot, M., Koterba, D., & Zeyland, J. (2026) · Cells · doi:10.3390/cells15121110
“CCR2 + macrophages have been identified in human failing hearts and associated with adverse remodelling [9], while SPP1-expressing macrophages have emerged as a conserved pro-fibrotic population across human inflammatory cardiomyopathies [30].”
InfluentialMorita, W., Suzuki, Y., Yuan, R., Rodeo, S. A., Park‐Min, K., & Ivashkiv, L. B. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.07.31.667715
Distinct fibrosis-associated macrophage subsets coordinate iron metabolism in pulmonary fibrosis
Nabeshima, H., Fukushima, K., Liu, Y., Motooka, D., Niitsu, T., Fukui, E., Ichii, M., Nii, T., Akamine, Y., Hamada, N., et al. (2026) · International Immunology · doi:10.1093/intimm/dxag017
Han, X., Yu, Y., Fan, Y., & Zhang, M. (2026) · Discover Oncology · doi:10.1007/s12672-026-05167-x
Vastrad, B. M., Pattanashetti, S., Patil, S., & Vastrad, C. M. (2026) · Research Square · doi:10.21203/rs.3.rs-10057610/v1
The role of macrophage-myofibroblast transition in the pathogenesis of multi-organ fibrosis
Guo, C., Cao, R., Liao, L., Zhao, J., Wang, T., Li, J. J., Zhang, Y., & Li, H. (2026) · Tissue and Cell · doi:10.1016/j.tice.2026.103702
Immunoregulatory properties of the human acellular amniotic membrane for diabetic wound healing
Cai, R., Xiang, Z., Huang, L.-J., Huang, Z., Zhuo, C.-J., Liu, K., Parolini, O., & Huang, Y. (2026) · iScience · doi:10.1016/j.isci.2026.116749
Zhao, B., Chen, X., Feng, S., Pang, J., Liu, H., Yang, H., Li, W., & Chen, H. (2026) · iScience · doi:10.1016/j.isci.2026.116734
Spatial transcriptomic analysis reveals spatial features in human Stanford type A aortic dissection
Li, Y., Cao, Y., Liu, F., Wang, L.-Y., Liu, H., Zhao, Q., Adi, D., Huo, Q., Liu, Z., Luo, J., et al. (2026) · iScience · doi:10.1016/j.isci.2026.116868
Li, Y. (2026) · Computational Biology and Chemistry · doi:10.1016/j.compbiolchem.2026.109287
Wu, Q., Gong, Q., Yuan, L., Li, Z., Ashenberg, O., Chen, F., Xavier, R. J., & Uhler, C. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.07.31.741265
Macrophages diverge into profibrotic SAMs and proresolving ReM2 cells to regulate liver fibrosis
Zhang, D., Liu, X., Ma, D., Liao, L., Duan, F., Wang, Y., Zhang, T., Liu, J., Dong, W., Jin, J. N., et al. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2611441123
Macrophage heterogeneity in organ fibrosis in the era of single-cell omics
Qiu, W.-H., Huang, Y., Chen, J.-Y., Chu, C.-L., Shen, Q.-Q., & Yan, J.-W. (2026) · Molecular Biology Reports · doi:10.1007/s11033-026-12723-9
Obana, M., Tomimatsu, M., Tanaka, S., Shirakura, K., Okada, Y., & Fujio, Y. (2026) · The Journal of Physiological Sciences · doi:10.1016/j.jphyss.2026.100107
- Authors
- Uhlig, M., Billig, S., Wienhold, J., & Schumacher, D.
- Affiliations
- RWTH Aachen University (DE)
- Corresponding author
- Uhlig, Moritz
- Venue
- Cells
- Publisher
- MDPI AG
- Published
- 2025-02-27
- Volume
- 14
- Issue
- 5
- Pages
- 345
- ISSN
- 2073-4409 (ISSN-L)
- PMC
- PMC11898914
- OpenAlex
- W4407992591
- Cited by
- 29
- References
- 58
- Citations by year
- 2026: 22 · 2025: 7
- FWCI
- 5.26
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cells (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion, other-oa)
- RWTH Publications (RWTH Aachen)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- myocardial fibrosis, SPP1+ macrophages, osteopontin, TREM2, macrophage heterogeneity, heart failure, extracellular matrix remodeling, myofibroblast activation, macrophage differentiation, platelet factor 4, GM-CSF, IL-17A, therapeutic target
- MeSH terms
- Animals, Fibrosis, Heart Diseases, Humans, Macrophages, Myocardium, Osteopontin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
