作者
Felix A Trogisch, Aya Abouissa, Merve Keles, Anne Birke, Manuela Fuhrmann, Gesine M Dittrich, Julio Cordero, Adel El Sherbiny, Abel Martin Garrido, Steve Grein, Luka Nicin, Sophia-Iris Bibli, Rannar Airik, Andreas Kispert, Ralf Kist, Sun Quanchao, Sina W Kürschner, Manuel Winkler, Norbert Gretz, Carolin Mogler, Thomas Korff, Philipp-Sebastian Koch, Stefanie Dimmeler, Gergana Dobreva, Joerg Heineke
发表日期
2023/8/4
期刊
Circulation Research
卷号
133
期号
Suppl_1
页码范围
AGS. 06-AGS. 06
出版商
Lippincott Williams & Wilkins
简介
Introduction: Endothelial cells (ECs) undergo mesenchymal activation (EndoMA) during the onset of fibrotic cardiac remodeling. The contribution of EndoMA to disease progression, matrix deposition and upstream master regulators, however, remain elusive.
Objective: Aim of the study was to investigate the impact of the fibrogenic transcription factor Sox9 in ECs on the development of fibrotic disease.
Methods & Results: Following both transverse aortic contriction (TAC) and administration of high fat diet (HFD) with NOS inhibitor L-NAME in mice, as well as in human diseased hearts, we found a significant induction of Sox9 in cardiac ECs. EC-specific overexpression of Sox9 in transgenic mice induced fibrotic and hypertrophic remodeling of heart, lung, liver and spleen, accompanied by left-ventricular diastolic followed by systolic dysfunction. Both bulk and single-cell (SC) RNA sequencing (seq) of isolated ECs as …
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FA Trogisch, A Abouissa, M Keles, A Birke… - Circulation Research, 2023