Research output: Contribution to journal › Article › peer-review
Notch-dependent EMT is attenuated in patients with aortic aneurysm and bicuspid aortic valve. / Kostina, Aleksandra S.; Uspensky, Vladimir E.; Irtyuga, Olga B.; Ignatieva, Elena V.; Freylikhman, Olga; Gavriliuk, Natalia D.; Moiseeva, Olga M.; Zhuk, Sergey; Tomilin, Alexey; Kostareva, Anna A.; Malashicheva, Anna B.
In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1862, No. 4, 04.2016, p. 733-740.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Notch-dependent EMT is attenuated in patients with aortic aneurysm and bicuspid aortic valve
AU - Kostina, Aleksandra S.
AU - Uspensky, Vladimir E.
AU - Irtyuga, Olga B.
AU - Ignatieva, Elena V.
AU - Freylikhman, Olga
AU - Gavriliuk, Natalia D.
AU - Moiseeva, Olga M.
AU - Zhuk, Sergey
AU - Tomilin, Alexey
AU - Kostareva, Anna A.
AU - Malashicheva, Anna B.
PY - 2016/4
Y1 - 2016/4
N2 - 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.
AB - 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.
KW - Aorta
KW - Endothelium
KW - Valves
KW - Signal transduction
KW - MESENCHYMAL TRANSITION
KW - DISEASE
KW - MUTATIONS
KW - GENE
KW - ACTIVATION
KW - MALFORMATIONS
KW - MECHANISMS
KW - DISORDERS
KW - VEGF
U2 - 10.1016/j.bbadis.2016.02.006
DO - 10.1016/j.bbadis.2016.02.006
M3 - статья
VL - 1862
SP - 733
EP - 740
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
SN - 0925-4439
IS - 4
ER -
ID: 7567534