Dokument: Purinergic signaling modulates endothelial-to-mesenchymal transition in human aortic valve endothelial cells
| Titel: | Purinergic signaling modulates endothelial-to-mesenchymal transition in human aortic valve endothelial cells | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=73371 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20260526-112743-7 | |||||||
| Kollektion: | Publikationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Texte » Artikel, Aufsatz | |||||||
| Medientyp: | Text | |||||||
| Autoren: | Schmidt, Vera [Autor] Weber, Andreas [Autor] Lichtenberg , Artur [Autor] Akhyari, Payam [Autor] Schrader, Jürgen [Autor] Martsch, Pascal [Autor] Barth, Mareike [Autor] | |||||||
| Dateien: |
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| Stichwörter: | Endothelial-mesenchymal transition , Calcific aortic valve disease , Ectonucleotidases , Human valvular endothelial cells , Purinergic signaling , Adenosine | |||||||
| Beschreibung: | Endothelial-to-mesenchymal transition (EndMT) is a phenotypic switch in which endothelial cells acquire mesenchymal characteristics, involving both functional and morphological changes. While EndMT is essential for cardiac development, its aberrant activation contributes to adult cardiovascular pathologies, including calcific aortic valve disease (CAVD). Dysregulation of ectonucleotidases—membrane-bound enzymes that regulate extracellular ATP and adenosine metabolism—has been implicated in such diseases. Altered extracellular nucleotide signaling influences valvular interstitial cell (VIC) degeneration and may interact with valvular endothelial cells (VECs) undergoing EndMT. The objective of this study was to investigate the role of the purinergic signaling system in regulating EndMT in human aortic VECs.
Primary human VECs were cultured in vitro and treated with inhibitors of ectonucleoside triphosphate diphosphohydrolase 1 (CD39), ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), and 5′-nucleotidase (CD73), alongside adenosine and P2 purinergic receptor agonists. EndMT markers and signaling pathways were assessed via phosphorylation assays and mRNA expression analysis of key transcription factors, including SLUG, SNAIL, ZEB1, and ZEB2. Inhibition of ATP- and AMP-hydrolyzing enzymes (CD39, ENPP1, CD73) enhanced p38 phosphorylation and modulated SLUG expression. Activation of P2 and adenosine A2B receptors altered SNAIL levels, while A2A receptor signaling influenced ZEB1 and ZEB2 expression. These perturbations resulted in pronounced morphological changes consistent with EndMT. In conclusion, dysregulation of the purinergic signaling system induces EndMT in human aortic VECs, highlighting a potential mechanistic link between extracellular nucleotide metabolism and valvular pathology. Targeting purinergic pathways may represent a therapeutic avenue for CAVD and related vascular disorders. | |||||||
| Rechtliche Vermerke: | Originalveröffentlichung:
Schmidt, V., Weber, A., Lichtenberg , A., Schrader, J., Martsch, P., Barth, M., & Akhyari, P. (2026). Purinergic signaling modulates endothelial-to-mesenchymal transition in human aortic valve endothelial cells. BBA Advances, 9, Article 100190. https://doi.org/10.1016/j.bbadva.2026.100190 | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 26.05.2026 | |||||||
| Dateien geändert am: | 26.05.2026 |
