{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:15:27Z","timestamp":1792631727298,"version":"4.5.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T00:00:00Z","timestamp":1646265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,17]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Atherosclerosis is a chronic inflammatory disease of the arteries leading to the formation of atheromatous plaques. Human mesenchymal stem cells (hMSCs) are recruited from the circulation into plaques where in response to their environment they adopt a phenotype with immunomodulatory properties. However, the mechanisms underlying hMSC function in these processes are unclear. Recently, we described that miRNA let-7f controls hMSC invasion guided by inflammatory cytokines and chemokines. Here, we investigated the role of let-7f in hMSC tropism to human atheromas and the effects of the plaque microenvironment on cell fate and release of soluble factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Incubation of hMSCs with LL-37, an antimicrobial peptide abundantly found in plaques, increased biosynthesis of let-7f and N-formyl peptide receptor 2 (FPR2), enabling chemotactic invasion of the cells towards LL-37, as determined by qRT-PCR, flow cytometry, and cell invasion assay analysis. In an Apoe\u2212\/\u2212 mouse model of atherosclerosis, circulating hMSCs preferentially adhered to athero-prone endothelium. This property was facilitated by elevated levels of let-7f in the hMSCs, as assayed by ex vivo artery perfusion and two-photon laser scanning microscopy. Exposure of hMSCs to homogenized human atheromatous plaque material considerably induced the production of various cytokines, chemokines, matrix metalloproteinases, and tissue inhibitors of metalloproteinases, as studied by PCR array and western blot analysis. Moreover, exposure to human plaque extracts elicited differentiation of hMSCs into cells of the myogenic lineage, suggesting a potentially plaque-stabilizing effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings indicate that let-7f promotes hMSC tropism towards atheromas through the LL-37\/FPR2 axis and demonstrate that hMSCs upon contact with human plaque environment develop a potentially athero-protective signature impacting the pathophysiology of atherosclerosis.<\/jats:p><\/jats:sec>","DOI":"10.1093\/cvr\/cvac022","type":"journal-article","created":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T22:10:02Z","timestamp":1646086202000},"page":"155-166","source":"Crossref","is-referenced-by-count":13,"title":["Properties and fate of human mesenchymal stem cells upon miRNA let-7f-promoted recruitment to atherosclerotic plaques"],"prefix":"10.1093","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4759-3408","authenticated-orcid":false,"given":"Virginia","family":"Egea","sequence":"first","affiliation":[{"name":"Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University of Munich , Munich , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9871-6696","authenticated-orcid":false,"given":"Remco Theodorus Adrianus","family":"Megens","sequence":"additional","affiliation":[{"name":"Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University of Munich , Munich , Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance , Munich , Germany"},{"name":"Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht, University of Maastricht , Maastricht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1811-4746","authenticated-orcid":false,"given":"Donato","family":"Santovito","sequence":"additional","affiliation":[{"name":"Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University of Munich , Munich , Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance , Munich , Germany"},{"name":"Institute for Genetic and Biomedical Research (IRGB), UoS of Milan, National Research Council (CNR) , Milan , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarawuth","family":"Wantha","sequence":"additional","affiliation":[{"name":"Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University of Munich , Munich , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Brandl","sequence":"additional","affiliation":[{"name":"St. Mary\u2019s Square Institute for Vascular Surgery and Phlebology , Munich , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0698-6416","authenticated-orcid":false,"given":"Wolfgang","family":"Siess","sequence":"additional","affiliation":[{"name":"Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University of Munich , Munich , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sajjad","family":"Khani","sequence":"additional","affiliation":[{"name":"Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University of Munich , Munich , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Soehnlein","sequence":"additional","affiliation":[{"name":"Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University of Munich , Munich , Germany"},{"name":"Department of Physiology and Pharmacology (FyFa), Karolinska Institutet , Stockholm , Sweden"},{"name":"Institute for Experimental Pathology (ExPat), Center for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms-University of Muenster , Muenster , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7840-3991","authenticated-orcid":false,"given":"Alexander","family":"Bartelt","sequence":"additional","affiliation":[{"name":"Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University of Munich , Munich , Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance , Munich , Germany"},{"name":"Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich , Neuherberg , Germany"},{"name":"Department of Molecular Metabolism, Sabri \u00dclker Center for Metabolic Research, Harvard T.H. 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