{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:23:20Z","timestamp":1786116200640,"version":"build-2736575974"},"reference-count":27,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>The pulmonary microvasculature plays an essential role in maintaining alveolar integrity, but the direct effects of inhaled corticosteroids (ICS) on pulmonary endothelial cell function remain poorly understood. We investigated the effects of budesonide, formoterol, and their combination on endothelial network formation, apoptosis, migration, proliferation, and efferocytosis using human pulmonary microvascular endothelial cells (HPMEC-ST1.6R), A549 alveolar epithelial cells, and phagocytic cell models. Budesonide, alone or combined with formoterol, altered endothelial network formation on Matrigel by reducing total tubule length and the number of junctions while increasing tubule thickness, indicating reduced branching complexity. Budesonide also decreased epithelial secretion of the pro-angiogenic mediators VEGF, IL-8, and MCP-1. An independent set of experiments showed that fluticasone propionate similarly reduced VEGF, IL-8, MCP-1, TNF-\u03b1, and IL-6, supporting a class effect of corticosteroids on the epithelial secretome. Despite reducing angiogenic responses, budesonide protected endothelial cells from apoptosis, reduced caspase-3\/7 activity, accelerated wound closure without affecting proliferation, preserved endothelial spheroid integrity, and enhanced efferocytosis. Formoterol alone had minimal effects and did not consistently enhance budesonide responses. Together, these in vitro findings suggest that, in the cell models studied, pulmonary endothelial responses to the ICS\/LABA combinations tested are determined predominantly by the corticosteroid component, which suppresses pro-angiogenic mediator secretion while preserving endothelial survival and repair. As an exploratory cell-based study, these observations are hypothesis-generating and require confirmation in primary cells and in vivo models before clinical inferences can be drawn.<\/jats:p>","DOI":"10.3390\/ijms27157045","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T08:08:02Z","timestamp":1786003682000},"page":"7045","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Endothelial Responses to ICS\/LABA Combinations Are Determined Primarily by the Corticosteroid Component"],"prefix":"10.3390","volume":"27","author":[{"given":"Bassam","family":"Redwan","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, Knappschaft Kliniken Gelsenkirchen Buer, 45894 Gelsenkirchen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Biancosino","sequence":"additional","affiliation":[{"name":"Helios University Hospital Wuppertal, University of Witten\/Herdecke, 42283 Wuppertal, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9980-0160","authenticated-orcid":false,"given":"Amir","family":"Mehdizadeh-Shrifi","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Hannover Medical School (MHH), 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix Nikolaus","family":"Lennartz","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Hannover Medical School (MHH), 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery and Lung Assist, Klinikum Ibbenb\u00fcren, 49477 Ibbenb\u00fcren, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"Wiebe","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, University Hospital of M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Schael","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Hannover Medical School (MHH), 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Zardo","sequence":"additional","affiliation":[{"name":"German Center for Lung Research (DZL), Biomedical Research in End-Stage and Obstructive Lung Disease (BREATH), 30625 Hannover, Germany"},{"name":"Department of Cardiothoracic, Transplantation and Vascular Surgery (Division of Thoracic Surgery), Hannover Medical School (MHH), 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7687-5258","authenticated-orcid":false,"given":"Sabina","family":"Janciauskiene","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Hannover Medical School (MHH), 30625 Hannover, Germany"},{"name":"German Center for Lung Research (DZL), Biomedical Research in End-Stage and Obstructive Lung Disease (BREATH), 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiko","family":"Golpon","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Hannover Medical School (MHH), 30625 Hannover, Germany"},{"name":"German Center for Lung Research (DZL), Biomedical Research in End-Stage and Obstructive Lung Disease (BREATH), 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2749","DOI":"10.1172\/JCI60324","article-title":"Pathogenesis of chronic obstructive pulmonary disease","volume":"122","author":"Tuder","year":"2012","journal-title":"J. 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