Mechanical strain triggers endothelial-to-mesenchymal transition of the endocardium in the immature heart

Background Endothelial-to-mesenchymal-transition (EndMT) plays a major role in cardiac fibrosis, including endocardial fibroelastosis but the stimuli are still unknown. We developed an endothelial cell (EC) culture and a whole heart model to test whether mechanical strain triggers TGF-β-mediated End...

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Veröffentlicht in:Pediatric research 2022-09, Vol.92 (3), p.721-728
Hauptverfasser: Vorisek, Carina, Weixler, Viktoria, Dominguez, Massiel, Axt-Fliedner, Roland, Hammer, Peter E., Lin, Ruei-Zeng, Melero-Martin, Juan M., del Nido, Pedro J., Friehs, Ingeborg
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Sprache:eng
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Zusammenfassung:Background Endothelial-to-mesenchymal-transition (EndMT) plays a major role in cardiac fibrosis, including endocardial fibroelastosis but the stimuli are still unknown. We developed an endothelial cell (EC) culture and a whole heart model to test whether mechanical strain triggers TGF-β-mediated EndMT. Methods Isolated ECs were exposed to 10% uniaxial static stretch for 8 h (stretch) and TGF-β-mediated EndMT was determined using the TGF-β-inhibitor SB431542 (stretch + TGF-β-inhibitor), BMP-7 (stretch + BMP-7) or losartan (stretch + losartan), and isolated mature and immature rats were exposed to stretch through a weight on the apex of the left ventricle. Immunohistochemical staining for double-staining with endothelial markers (VE-cadherin, PECAM1) and mesenchymal markers (αSMA) or transcription factors (SLUG/SNAIL) positive nuclei was indicative of EndMT. Results Stretch-induced EndMT in ECs expressed as double-stained ECs/total ECs (cells: 46 ± 13%; heart: 15.9 ± 2%) compared to controls (cells: 7 ± 2%; heart: 3.1 ± 0.1; p  
ISSN:0031-3998
1530-0447
DOI:10.1038/s41390-021-01843-6