title: Upregulation of the high mobility group AT-hook 2 gene in acute aortic dissection is potentially associated with endothelial-mesenchymal transition.
abstract: The high mobility group AT-hook 2 (HMGA2) gene is proposed to regulate the genes involved in the epithelial-mesenchymal transition (EMT). One form of EMT is endothelial-mesenchymal transition (EndMT). We analyzed the expression profile of the HMGA2 gene in different human aortic diseases. Aortic specimens were collected from 51 patients, including 19 with acute aortic dissection, 26 with aortic aneurysm, two with Marfan syndrome and four aortic valves. Quantitative real-time polymerase chain reaction was carried out for HMGA2 and immunohistochemical analyses were performed for HMGA2, SNAI1, Vimentin, CD34, MKI-67 and TGFB1. The expression of let-7d microRNA, which is assumed to play a role in the regulation of HMGA2, was also quantified. The level of HMGA2 gene expression was significantly higher in acute aortic dissection compared with all the other samples (193.1 vs. 8.1 fold normalized to calibrator, P<0.001). The immunohistochemical investigation showed that HMGA2, SNAI1, and Vimentin proteins were mainly detected in the endothelial cells of the vasa vasorum. The HMGA2 gene is upregulated in acute aortic dissection. This is the first report describing a link between HMGA2 and acute aortic dissection. The HMGA2, SNAI1 and Vimentin proteins were mainly detected in the endothelium of the vasa vasorum. It seems that HMGA2 overexpression in acute aortic dissection occurs in a let-7d-independent manner and is associated with EndMT of the vasa vasorum.
authors.affiliation: Center for Human Genetics, University of Bremen, Bremen, Germany.
authors.forename: Gazanfer
authors.initials: G
authors.lastname: Belge
authors.forename: Arlo
authors.initials: A
authors.lastname: Radtke
authors.forename: Anke
authors.initials: A
authors.lastname: Meyer
authors.forename: Isabel
authors.initials: I
authors.lastname: Stegen
authors.forename: Doreen
authors.initials: D
authors.lastname: Richardt
authors.forename: Rolf
authors.initials: R
authors.lastname: Nimzyk
authors.forename: Vishal
authors.initials: V
authors.lastname: Nigam
authors.forename: Andreas
authors.initials: A
authors.lastname: Dendorfer
authors.forename: Hans H
authors.initials: HH
authors.lastname: Sievers
authors.forename: Markus
authors.initials: M
authors.lastname: Tiemann
authors.forename: Igor
authors.initials: I
authors.lastname: Buchwalow
authors.forename: Joern
authors.initials: J
authors.lastname: Bullerdiek
authors.forename: Salah A
authors.initials: SA
authors.lastname: Mohamed
mesh_terms: D000328:Adult; D000784:Aortic Dissection / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D001014:Aortic Aneurysm / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D025743:HMGA2 Protein / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation; D014651:Vasa Vasorum / Q000378:metabolism / Q000473:pathology; D014746:Vimentin / Q000378:metabolism
chemical_list: D025743:HMGA2 Protein; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D014746:Vimentin