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

Biochimica Et Biophysica Acta
Aleksandra S KostinaAnna Malashicheva

Abstract

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 bi...Continue Reading

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Citations

Oct 19, 2017·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·K PerepelinaA Malashicheva
Dec 19, 2017·Cell Transplantation·Daria KostinaAnna Malashicheva
Jul 28, 2018·Cardiovascular Research·Juliette RaffortZiad Mallat
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Dec 10, 2019·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Anna MalashichevaVladimir Uspensky
Sep 3, 2018·Atherosclerosis. Supplements·Aleksandra KostinaAnna Malashicheva
Jul 3, 2021·Biomedicines·Aleksandra KostinaAnna Malashicheva
Aug 9, 2019·Current Cardiology Reviews·Taha AnbaraNahid Aboutaleb

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