{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:47:43Z","timestamp":1792640863899,"version":"4.5.0"},"reference-count":35,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T00:00:00Z","timestamp":1618531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cardiac sarcoidosis (CS) is a poorly understood disease and is characterized by the focal accumulation of immune cells, thus leading to the formation of granulomata (GL). To identify the developmental principles of fatal GL, fluorescence microscopy and Western blot analysis of CS and control patients is presented here. CS is visualized macroscopically by positron emission tomography (PET)\/ computed tomography (CT). A battery of antibodies is used to determine structural, cell cycle and inflammatory markers. GL consist of CD68+, CD163+ and CD206+ macrophages surrounded by T-cells within fibrotic areas. Cell cycle markers such as phospho-histone H3, phospho-Aurora and Ki67 were moderately present; however, the phosphorylated ERM (ezrin, radixin and moesin) and Erk1\/2 proteins, strong expression of the myosin motor protein and the macrophage transcription factor PU.1 indicate highly active GL. Mild apoptosis is consistent with PI3 kinase and Akt activation. Massive amounts of the IL-1R antagonist reflect a mild activation of stress and inflammatory pathways in GL. High levels of oncostatin M and the Reg3A and Reg3\u03b3 chemokines are in accordance with macrophage accumulation in areas of remodeling cardiomyocytes. We conclude that the formation of GL occurs mainly through chemoattraction and less by proliferation of macrophages. Furthermore, activation of the oncostatin\/Reg3 axis might help at first to wall-off substances but might initiate the chronic development of heart failure.<\/jats:p>","DOI":"10.3390\/ijms22084148","type":"journal-article","created":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T10:20:11Z","timestamp":1618568411000},"page":"4148","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Myocardial Accumulations of Reg3A, Reg3\u03b3 and Oncostatin M Are Associated with the Formation of Granulomata in Patients with Cardiac Sarcoidosis"],"prefix":"10.3390","volume":"22","author":[{"given":"Praveen","family":"Gajawada","sequence":"first","affiliation":[{"name":"Department of Cardiac Surgery, Kerckhoff Heart Center, Benekestr. 2-8, 61231 Bad Nauheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayse","family":"Cetinkaya","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Kerckhoff Heart Center, Benekestr. 2-8, 61231 Bad Nauheim, Germany"},{"name":"Campus Kerckhoff, Justus-Liebig-University Giessen, 61231 Bad Nauheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"von Gerlach","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum Giessen und Marburg GmbH, Standort Marburg, Baldingerstr., 35033 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Kubin","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Kerckhoff Heart Center, Benekestr. 2-8, 61231 Bad Nauheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9832-0285","authenticated-orcid":false,"given":"Heiko","family":"Burger","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Kerckhoff Heart Center, Benekestr. 2-8, 61231 Bad Nauheim, Germany"},{"name":"Campus Kerckhoff, Justus-Liebig-University Giessen, 61231 Bad Nauheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"N\u00e4bauer","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik I, Klinikum der Universit\u00e4t M\u00fcnchen, Marchioninistr. 15, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carola","family":"Grinninger","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik I, Klinikum der Universit\u00e4t M\u00fcnchen, Marchioninistr. 15, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Rolf","sequence":"additional","affiliation":[{"name":"Campus Kerckhoff, Justus-Liebig-University Giessen, 61231 Bad Nauheim, Germany"},{"name":"Department of Cardiology, Kerckhoff Heart and Lung Center, Benekestr. 2-8, 61231 Bad Nauheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Sch\u00f6nburg","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Kerckhoff Heart Center, Benekestr. 2-8, 61231 Bad Nauheim, Germany"},{"name":"Campus Kerckhoff, Justus-Liebig-University Giessen, 61231 Bad Nauheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeong-Hoon","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Kerckhoff Heart Center, Benekestr. 2-8, 61231 Bad Nauheim, Germany"},{"name":"Campus Kerckhoff, Justus-Liebig-University Giessen, 61231 Bad Nauheim, Germany"},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site RhineMain, 60549 Frankfurt\/Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kubin","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Kerckhoff Heart Center, Benekestr. 2-8, 61231 Bad Nauheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6239-3503","authenticated-orcid":false,"given":"Manfred","family":"Richter","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Kerckhoff Heart Center, Benekestr. 2-8, 61231 Bad Nauheim, Germany"},{"name":"Campus Kerckhoff, Justus-Liebig-University Giessen, 61231 Bad Nauheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.jacc.2016.03.605","article-title":"Cardiac Sarcoidosis","volume":"68","author":"Birnie","year":"2016","journal-title":"J. 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