{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:48:50Z","timestamp":1788544130718,"version":"build-2803163510"},"reference-count":64,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T00:00:00Z","timestamp":1641945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004955","name":"Austrian Research Promotion Agency","doi-asserted-by":"publisher","award":["862068"],"award-info":[{"award-number":["862068"]}],"id":[{"id":"10.13039\/501100004955","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Pulmonary hypertension (PH) is characterized by increased pulmonary arterial pressure caused by the accumulation of mesenchymal-like cells in the pulmonary vasculature. PH can lead to right ventricular hypertrophy (RVH) and, ultimately, heart failure and death. In PH etiology, endothelial-to-mesenchymal transition (EndMT) has emerged as a critical process governing the conversion of endothelial cells into mesenchymal cells, and S100A4, EGF, and EGFR are implicated in EndMT. However, a potential role of S100A4, EGF, and EGFR in PH has to date not been elucidated. We therefore quantified S100A4, EGF, and EGFR in patients suffering from chronic thromboembolic pulmonary hypertension (CTEPH) and idiopathic pulmonary arterial hypertension (iPAH). To determine specificity for unilateral heart disease, the EndMT biomarker signature was further compared between PH patients presenting with RVH and patients suffering from aortic valve stenosis (AVS) with left ventricular hypertrophy. Reduced S100A4 concentrations were found in CTEPH and iPAH patients with RVH. Systemic EGF was increased in CTEPH but not in iPAH, while AVS patients displayed slightly diminished EGF levels. EGFR was downregulated in all patient groups when compared to healthy controls. Longitudinal data analysis revealed no effect of surgical therapies on EndMT markers. Pulmonary thrombo-endarterectomized samples were devoid of S100A4, while S100A4 tissue expression positively correlated with higher grades of Heath\u2013Edwards histopathological lesions of iPAH-derived lung tissue. Histologically, EGFR was not detectable in CTEPH lungs or in iPAH lesions. Together, our data suggest an intricate role for S100A4 and EGF\/EGFR in PH with right heart pathology.<\/jats:p>","DOI":"10.3390\/biology11010118","type":"journal-article","created":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T09:10:36Z","timestamp":1641978636000},"page":"118","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Roles of S100A4 and the EGF\/EGFR Signaling Axis in Pulmonary Hypertension with Right Ventricular Hypertrophy"],"prefix":"10.3390","volume":"11","author":[{"given":"Maria","family":"Laggner","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Applied Immunology Laboratory, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Hacker","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, University Hospital St. P\u00f6lten, 3100 St. P\u00f6lten, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicitas","family":"Oberndorfer","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3328-7795","authenticated-orcid":false,"given":"Jonas","family":"Bauer","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Raunegger","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine and Cardiology, Klinikum Klagenfurt am W\u00f6rthersee, 9020 Klagenfurt, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Gerges","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Division of Cardiology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e1s","family":"Szerafin","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9893-5485","authenticated-orcid":false,"given":"J\u00fcrgen","family":"Thanner","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Division of Cardiology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nika","family":"Skoro-Sajer","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Division of Cardiology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik Jan","family":"Ankersmit","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Applied Immunology Laboratory, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6037-5475","authenticated-orcid":false,"given":"Bernhard","family":"Moser","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2002828","DOI":"10.1183\/13993003.02828-2020","article-title":"ERS statement on chronic thromboembolic pulmonary hypertension","volume":"57","author":"Delcroix","year":"2021","journal-title":"Eur. 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