{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T20:31:25Z","timestamp":1782160285574,"version":"3.54.5"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Viral myocarditis is characterized by inflammatory cell infiltration and myocardial damage. However, the involvement of immune cells and the interaction between immune cells and stromal cells remain poorly understood. We successfully established a mouse model of viral myocarditis induced by Coxsackievirus B3 (CVB3) and systematically analyzed immune cell infiltration and myocardial injury at different time points. Single\u2010cell RNA sequencing (scRNA\u2010seq) was performed at the peak of immune cell infiltration to characterize the immune landscape of infected cardiac tissue and peripheral blood mononuclear cells (PBMCs). Macrophage depletion and vascular endothelial growth factor receptor (VEGFR) inhibition were performed to validate the immune\u2010stromal crosstalk. Peak immune cell infiltration and myocardial injury occurred on the 7th day of infection. scRNA\u2010seq revealed that endothelial cells and mononuclear phagocytes (MNPs) were the most substantially expanded cell populations in the hearts of mice with viral infection. Trem2 macrophage, characterized by tissue repair gene signatures, was the predominant MNP subcluster in the infected heart, while tip cells and capillaries were the most expanded endothelial cell clusters. Cell\u2013cell communication analysis identified increased macrophage\u2013endothelial cell interactions during CVB3 infection. Macrophage\u2010derived VEGFA secretion, partially induced by CVB3 infection and apoptotic cardiomyocyte debris, promoted angiogenesis, while macrophage depletion resulted in reduced VEGFA secretion and endothelial proliferation. Moreover, inhibition of VEGFR exacerbated cardiac dysfunction, highlighting the protective role of angiogenesis in myocarditis progression. In summary, these results elucidated a cardioprotective role of macrophage\u2010driven angiogenesis via vascular endothelial growth factor signaling during viral myocarditis, providing new insights into therapeutic strategies for inflammatory heart diseases.<\/jats:p>","DOI":"10.1002\/jmv.70440","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T07:15:16Z","timestamp":1750144516000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Single\u2010Cell RNA Sequencing Reveals Macrophage\u2013Endothelial Cell Crosstalk in Viral Myocarditis"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5139-2977","authenticated-orcid":false,"given":"Yingnan","family":"You","sequence":"first","affiliation":[{"name":"Department of Pediatric Cardiology Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiyin","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan China"},{"name":"School of Medicine, Cheeloo College of Medicine Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjie","family":"Ma","sequence":"additional","affiliation":[{"name":"Shandong First Medical University &amp; Shandong Academy of Medical Sciences Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuyun","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan China"},{"name":"School of Medicine, Cheeloo College of Medicine Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxue","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan China"},{"name":"School of Medicine, Cheeloo College of Medicine Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjie","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Medicine, Cheeloo College of Medicine Shandong University Jinan China"},{"name":"Department of Pediatrics The Affiliated Taian City Central Hospital of Qingdao University Tai'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailin","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan China"},{"name":"Shandong First Medical University &amp; 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