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Cited by 19Viral Infections and Immunology ResearchCardiac Fibrosis and RemodelingAtherosclerosis and Cardiovascular Diseases

Macrophage-derived SPP1 exacerbate myocardial injury by interacting with fibroblasts in viral myocarditis

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Duan, Xiuyun, Zhang, Li, Liu, Keyu, Guo, Kaiyin, You, Yingnan, Jia, Hailin, Zhou, Shan, Han, Bo·2025·Biology Direct
DOI 10.1186/s13062-025-00621-2PMC PMC11907792
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Abstract

BACKGROUND: Viral myocarditis (VMC) is an inflammatory myocardial condition triggered by viral infections which involves pathogenic-related damage and immune-mediated damage. However, the precise immunopathogenic mechanisms underlying VMC remain elusive. METHODS: We performed single-cell RNA sequencing on mouse hearts during the acute phase of CVB3-induced VMC. After manually annotating cell types, functional analyses of macrophage were performed by cell ratio changes, customized gene set module scoring and CellPhoneDB. Utilizing indirect co-culture experiments in vitro, the effects of macrophage-derived SPP1 on cardiac fibroblasts were investigated. Depletion of macrophages and inhibition of SPP1 expression in mice were carried out to study the effects of macrophage-derived SPP1 on cardiac function, inflammation levels, and myocardial injury in mice with VMC. RESULTS: macrophages communicate extensively with fibroblasts during VMC, and that SPP1 promotes fibroblast conversion to an inflammatory phenotype with high Ccl2/Ccl7 expression. This in turn increases monocyte chemotaxis to the heart. Besides, a partial depletion of macrophages in the early stages of VMC attenuated myocardial inflammation and myocardial injury in mice. Inhibition of SPP1 reduced cardiac macrophage infiltration, attenuated myocardial inflammation, and improved cardiac function in VMC mice. CONCLUSION: macrophages could self-recruit, and macrophage-derived SPP1 exacerbated myocardial immune injury by promoting high Ccl2/Ccl7 expression in fibroblasts. Our study advances understandings of VMC pathogenesis, and provides novel insight into potential immunotherapies for VMC.

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Authors
Duan, X., Zhang, L., Liu, K., Guo, K., You, Y., Jia, H., Zhou, S., & Han, B.
Affiliations
  • Shandong University (CN)
  • Ruijin Hospital (CN)
  • Shandong Provincial Hospital (CN)
Corresponding author
Han, Bo
ORCID
Venue
Biology Direct
Publisher
Springer Science and Business Media LLC
Published
2025-03-14
Volume
20
Issue
1
Pages
30-30
ISSN
1745-6150 (ISSN-L)
DOI
10.1186/s13062-025-00621-2
PMC
PMC11907792
OpenAlex
W4408457658
Cited by
19
References
4
Citations by year
2026: 13 · 2025: 6
FWCI
13.27
Type
journal article
Language
en
Open access
Licence
Locations
  • Biology Direct (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Natural Science Foundation of Shandong Province (ZR2023QH296, ZR2023MH052)
  • Jinan Science and Technology Bureau (202134015)
  • Taishan Scholar Foundation of Shandong Province (201511099)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Keywords
viral myocarditis, macrophages, osteopontin, cardiac fibroblasts, macrophage-fibroblast interaction, monocyte chemotaxis, myocarditis, myocardial injury, co-culture, macrophage depletion, factor V, factor VIII, coagulation factor IX, CO
MeSH terms
Animals, Coxsackievirus Infections, Fibroblasts, Macrophages, Male, Mice, Inbred C57BL, Myocarditis, Myocardium, Chemokine CCL2, Enterovirus B, Human, Mice, Osteopontin, Chemokine CCL7

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