{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:04:58Z","timestamp":1790816698021,"version":"4.1.0"},"reference-count":35,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T00:00:00Z","timestamp":1636675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Center of cardiovascular research","award":["81Z0710108; 81X2710142; 81X2400121"],"award-info":[{"award-number":["81Z0710108; 81X2710142; 81X2400121"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB-TR19; TP-A2"],"award-info":[{"award-number":["SFB-TR19; TP-A2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fibroblasts contribute to approximately 20% of the non-cardiomyocytic cells in the heart. They play important roles in the myocardial adaption to stretch, inflammation, and other pathophysiological conditions. Fibroblasts are a major source of extracellular matrix (ECM) proteins whose production is regulated by cytokines, such as TNF-\u03b1 or TGF-\u03b2. The resulting myocardial fibrosis is a hallmark of pathological remodeling in dilated cardiomyopathy (DCM). Therefore, in the present study, the secretome and corresponding transcriptome of human cardiac fibroblasts from patients with DCM was investigated under normal conditions and after TNF-\u03b1 or TGF-\u03b2 stimulation. Secreted proteins were quantified via mass spectrometry and expression of genes coding for secreted proteins was analyzed via Affymetrix Transcriptome Profiling. Thus, we provide comprehensive proteome and transcriptome data on the human cardiac fibroblast\u2019s secretome. In the secretome of quiescent fibroblasts, 58% of the protein amount belonged to the ECM fraction. Interestingly, cytokines were responsible for 5% of the total protein amount in the secretome and up to 10% in the corresponding transcriptome. Furthermore, cytokine gene expression and secretion were upregulated upon TNF-\u03b1 stimulation, while collagen secretion levels were elevated after TGF-\u03b2 treatment. These results suggest that myocardial fibroblasts contribute to pro-fibrotic and to inflammatory processes in response to extracellular stimuli.<\/jats:p>","DOI":"10.3390\/ijms222212262","type":"journal-article","created":{"date-parts":[[2021,11,14]],"date-time":"2021-11-14T20:48:36Z","timestamp":1636922916000},"page":"12262","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Cytokine-Mediated Alterations of Human Cardiac Fibroblast\u2019s Secretome"],"prefix":"10.3390","volume":"22","author":[{"given":"Hanna","family":"Br\u00e4uninger","sequence":"first","affiliation":[{"name":"Department of Cardiology, University Heart & Vascular Centre, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg\/Kiel\/L\u00fcbeck, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3862-1702","authenticated-orcid":false,"given":"Tilo","family":"Thottakara","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Heart & Vascular Centre, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg\/Kiel\/L\u00fcbeck, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9801-7972","authenticated-orcid":false,"given":"Jacob","family":"Sch\u00f6n","sequence":"additional","affiliation":[{"name":"Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Felix-Hausdorff-Str. 8, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svenja","family":"Voss","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Heart & Vascular Centre, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg\/Kiel\/L\u00fcbeck, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6808-3186","authenticated-orcid":false,"given":"Vishnu","family":"Dhople","sequence":"additional","affiliation":[{"name":"Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Felix-Hausdorff-Str. 8, 17475 Greifswald, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svenja","family":"Warnke","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Heart & Vascular Centre, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3237-140X","authenticated-orcid":false,"given":"Katharina","family":"Scherschel","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Heart & Vascular Centre, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany"},{"name":"Division of Cardiology (cNEP), EVK, 40217 D\u00fcsseldorf, Germany"},{"name":"Medical Faculty, Institute of Neural and Sensory Physiology, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt","family":"Schrage","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Heart & Vascular Centre, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg\/Kiel\/L\u00fcbeck, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1881-0197","authenticated-orcid":false,"given":"Paulus","family":"Kirchhof","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Heart & Vascular Centre, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg\/Kiel\/L\u00fcbeck, 20246 Hamburg, Germany"},{"name":"Institute of Cardiovascular Sciences, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Blankenberg","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Heart & Vascular Centre, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg\/Kiel\/L\u00fcbeck, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5689-3448","authenticated-orcid":false,"given":"Uwe","family":"V\u00f6lker","sequence":"additional","affiliation":[{"name":"Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Felix-Hausdorff-Str. 8, 17475 Greifswald, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Westermann","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Heart & Vascular Centre, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg\/Kiel\/L\u00fcbeck, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1507-0402","authenticated-orcid":false,"given":"Elke","family":"Hammer","sequence":"additional","affiliation":[{"name":"Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Felix-Hausdorff-Str. 8, 17475 Greifswald, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, 17475 Greifswald, 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