Notch-dependent EMT is attenuated in patients with aortic aneurysm and bicuspid aortic valve

Aleksandra S. Kostina, Vladimir E. Uspensky, Olga B. Irtyuga, Elena V. Ignatieva, Olga Freylikhman, Natalia D. Gavriliuk, Olga M. Moiseeva, Sergey Zhuk, Alexey Tomilin, Anna A. Kostareva, Anna B. Malashicheva

Результат исследований: Научные публикации в периодических изданияхстатья

37 Цитирования (Scopus)

Аннотация

Bicuspid aortic valve is the most common congenital heart malformation and the reasons for the aortopathies associated with bicuspid aortic valve remain unclear. NOTCH1 mutations are associated with bicuspid aortic valve and have been found in individuals with various left ventricular outflow tract abnormalities. Notch is a key signaling during cardiac valve formation that promotes the endothelial-to-mesenchymal transition. We address the role of Notch signaling in human aortic endothelial cells from patients with bicuspid aortic valve and aortic aneurysm. Aortic endothelial cells were isolated from tissue fragments of bicuspid aortic valve associated thoracic aortic aneurysm patients and from healthy donors. Endothelial-to-mesenchymal transition was induced by activation of Notch signaling. Effectiveness of the transition was estimated by loss of endothelial and gain of mesenchymal markers by immunocytochemistry and qPCR. We show that aortic endothelial cells from the patients with aortic aneurysm and bicuspid aortic valve have down regulated Notch signaling and fail to activate Notch-dependent endothelial-to-mesenchymal transition in response to its stimulation by different Notch ligands. Our findings support the idea that bicuspid aortic valve and associated aortic aneurysm is associated with dysregulation of the entire Notch signaling pathway independently on the specific gene mutation. (C) 2016 Elsevier B.V. All rights reserved.

Язык оригиналаАнглийский
Страницы (с-по)733-740
Число страниц8
ЖурналBiochimica et Biophysica Acta - Molecular Basis of Disease
Том1862
Номер выпуска4
DOI
СостояниеОпубликовано - апр 2016

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