Endothelial to mesenchymal transition in cardiovascular diseases: molecular insights and clinical perspectives.
| Title: | Endothelial to mesenchymal transition in cardiovascular diseases: molecular insights and clinical perspectives. |
|---|---|
| Authors: | Hall IF; Centre for Cardiovascular Science, Queens Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.; Aikawa E; Center for Excellence in Vascular Biology, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Center for Interdisciplinary Cardiovascular Sciences, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Sluimer J; Centre for Cardiovascular Science, Queens Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.; Department of Pathology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands.; Department of Medical Clinic II for Kidney and Hypertension Diseases, Rheumatological and Immunological Diseases, Rheinisch-Westfälische Technische Hochschule, Aachen, Germany.; Baker AH; Centre for Cardiovascular Science, Queens Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.; Department of Pathology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands.; Kovacic JC; Victor Chang Cardiac Research Institute, 405 Liverpool St., Darlinghurst, NSW 2010, Australia.; St. Vincent's Clinical School, The University of New South Wales, 390 Victoria St., Darlinghurst, NSW 2010, Australia.; School of Human Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia.; Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029, USA. |
| Source: | European heart journal [Eur Heart J] 2026 Mar 09; Vol. 47 (10), pp. 1144-1158. |
| Publication Type: | Journal Article; Review |
| Language: | English |
| Journal Info: | Publisher: Oxford University Press Country of Publication: England NLM ID: 8006263 Publication Model: Print Cited Medium: Internet ISSN: 1522-9645 (Electronic) Linking ISSN: 0195668X NLM ISO Abbreviation: Eur Heart J Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2005- : Oxford : Oxford University Press; Original Publication: London, Saunders [etc.] |
| MeSH Terms: | Cardiovascular Diseases*/pathology ; Cardiovascular Diseases*/physiopathology ; Epithelial-Mesenchymal Transition*/physiology ; Endothelial Cells*/physiology; Transforming Growth Factor beta/physiology ; Signal Transduction/physiology ; Humans ; Animals ; Mice |
| Abstract: | Endothelial to mesenchymal transition (EndMT) is a process whereby endothelial cells transition to adopt a mesenchymal-like fate, e.g. to become smooth muscle cells, osteoblasts, fibroblasts, or chondrocytes. In embryonic heart development, the importance of EndMT was established several decades ago, with ECs undergoing EndMT to give rise to the endocardial cushions that ultimately develop into the cardiac valves. More recently, EndMT has been observed in various adult cardiovascular diseases. This has been established through the application of state-of-the-art research tools, including cell lineage tracing in mice and single cell RNA sequencing, which have allowed in depth profiling of endothelial cells that have undergone transition to a mesenchymal-like state. As with any emerging field, certain challenges have arisen, such as the lack of a standardized definition of what constitutes EndMT at a molecular level and obtaining proof in humans that EndMT is mechanistically involved in the pathophysiology of cardiovascular diseases. The greatest evidence for the presence of cells undergoing EndMT in the adult exists for transplant vasculopathy, pulmonary arterial hypertension, vein graft remodeling, atherosclerosis, and valvular heart disease. The transforming growth factor beta pathway is the major driver, but this is not the exclusive signalling mechanism governing this complex process. Translational large animal studies have already been undertaken to inhibit EndMT in both valvular heart disease and vein graft remodeling, with positive results. These studies pave the way towards first-in-human clinical inhibition of EndMT as a therapeutic strategy. Here we review this exciting field, with particular emphasis on the functional role of EndMT in adult cardiovascular diseases using atherosclerosis and valvular disease as exemplars.; (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology.) |
| Grant Information: | R01HL148167 United States NH NIH HHS; R01HL174066 United States NH NIH HHS; RG194194 New South Wales Health; Snow Medical, The Bourne Foundation; SCAD Research Inc; Agilent; RE/24/130012 BHF Research Excellence; CH/11/2/28733 British Heart Foundation Chair of Translational Sciences; RG/F/24/110149 British Heart Foundation Chair of Translational Sciences; 551279788 Deutsch Forschungsgemeinschaft; 22RAF02 Leducq Foundation; GR 1000131 Pfizer; FS/IPBSRF/22/27050 United Kingdom BHF_ British Heart Foundation; APP43780 International ERC_ European Research Council; VIDI 016186364 Netherlands NWO_ Dutch Research Council; VICI 09150182410051 Netherlands NWO_ Dutch Research Council |
| Contributed Indexing: | Keywords: Atherosclerosis; EndMT; EndoMT; Endothelial; Endothelial to mesenchymal transition; Fibroblast; Plasticity; Smooth muscle cell; Valvular disease |
| Substance Nomenclature: | 0 (Transforming Growth Factor beta) |
| Entry Date(s): | Date Created: 20251023 Date Completed: 20260308 Latest Revision: 20260327 |
| Update Code: | 20260406 |
| PubMed Central ID: | PMC13016786 |
| DOI: | 10.1093/eurheartj/ehaf670 |
| PMID: | 41128016 |
| Database: | MEDLINE |
Journal Article; Review