title: Snail Is a Direct Target of Hypoxia-inducible Factor 1α (HIF1α) in Hypoxia-induced Endothelial to Mesenchymal Transition of Human Coronary Endothelial Cells.
abstract: Endothelial to mesenchymal transition (EndMT) was originally described in heart development where the endocardial endothelial cells that line the atrioventricular canal undergo an EndMT to form the endocardial mesenchymal cushion that later gives rise to the septum and mitral and tricuspid valves. In the postnatal heart specifically, endothelial cells that originate from the endocardium maintain increased susceptibility to undergo EndMT as remnants from their embryonic origin. Such EndMT involving adult coronary endothelial cells contributes to microvascular rarefaction and subsequent chronification of hypoxia in the injured heart, ultimately leading to cardiac fibrosis. Although in most endothelial beds hypoxia induces tip cell formation and sprouting angiogenesis, here we demonstrate that hypoxia is a stimulus for human coronary endothelial cells to undergo phenotypic changes reminiscent of EndMT via a mechanism involving hypoxia-inducible factor 1α-induced activation of the EndMT master regulatory transcription factor SNAIL. Our study adds further evidence for the unique susceptibility of endocardium-derived endothelial cells to undergo EndMT and provides novel insights into how hypoxia contributes to progression of cardiac fibrosis. Additional studies may be required to discriminate between distinct sprouting angiogenesis and EndMT responses of different endothelial cells populations.
authors.affiliation: From the Departments of Cardiology and Pneumology and.
authors.forename: Xingbo
authors.initials: X
authors.lastname: Xu
authors.affiliation: From the Departments of Cardiology and Pneumology and.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Tan
authors.affiliation: Nephrology and Rheumatology, University Medical Center of Göttingen, Georg August University, 37075 Göttingen, Germany and.
authors.forename: Björn
authors.initials: B
authors.lastname: Tampe
authors.affiliation: From the Departments of Cardiology and Pneumology and.
authors.forename: Elisa
authors.initials: E
authors.lastname: Sanchez
authors.affiliation: Nephrology and Rheumatology, University Medical Center of Göttingen, Georg August University, 37075 Göttingen, Germany and.
authors.forename: Michael
authors.initials: M
authors.lastname: Zeisberg
authors.affiliation: From the Departments of Cardiology and Pneumology and DZHK (German Centre for Cardiovascular Research) partner site, 37075 Göttingen, Germany elisabeth.zeisberg@med.uni-goettingen.de.
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Zeisberg
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004699:Endocardium / Q000166:cytology / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors
keywords: endothelial cell; fibroblast; fibrosis; hypoxia; hypoxia-inducible factor (HIF)