Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
Notch, BMP and WNT/beta-catenin network is impaired in endothelial cells of the patients with thoracic aortic aneurysm. / Kostina, Aleksandra; Bjork, Hanna; Ignatieva, Elena; Irtyuga, Olga; Uspensky, Vladimir; Semenova, Daria; Maleki, Shohreh; Tomilin, Alexey; Moiseeva, Olga; Franco-Cereceda, Anders; Gordeev, Mikhail; Faggian, Giuseppe; Kostareva, Anna; Eriksson, Per; Malashicheva, Anna.
в: Atherosclerosis Supplements, Том 35, 01.09.2018, стр. e6-e13.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - Notch, BMP and WNT/beta-catenin network is impaired in endothelial cells of the patients with thoracic aortic aneurysm
AU - Kostina, Aleksandra
AU - Bjork, Hanna
AU - Ignatieva, Elena
AU - Irtyuga, Olga
AU - Uspensky, Vladimir
AU - Semenova, Daria
AU - Maleki, Shohreh
AU - Tomilin, Alexey
AU - Moiseeva, Olga
AU - Franco-Cereceda, Anders
AU - Gordeev, Mikhail
AU - Faggian, Giuseppe
AU - Kostareva, Anna
AU - Eriksson, Per
AU - Malashicheva, Anna
PY - 2018/9/1
Y1 - 2018/9/1
N2 - Cellular and molecular mechanisms of thoracic aortic aneurysm are still not clear and therapeutic approaches are mostly absent. The role of endothelial cells in aortic wall integrity is emerging from recent studies. Although Notch pathway ensures endothelial development and integrity, and NOTCH1 mutations have been associated with thoracic aortic aneurysms, the role of this pathway in aneurysm remains elusive. The purpose of the present work was to study functions of Notch genes in endothelial cells of patients with sporadic thoracic aortic aneurysm.Aortic endothelial cells were isolated from aortic tissue of patients with thoracic aortic aneurysm and healthy donors. Gene expression of Notch and related BMP and WNT/beta-catenin pathways was estimated by qPCR; WNT/beta-catenin signaling was studied by TCF-luciferase reporter. To study the stress-response the cells were subjected to laminar shear stress and the expression of corresponding genes was estimated by qPCR.Analyses of mRNA expression of Notch genes, Notch target genes and Notch related pathways showed that endothelial cells of aneurysm patients have dysregulated Notch/BMP/WNT pathways compared to donor cells. Activity of Wnt pathway was significantly elevated in endothelial cells of the patients. Cells from patients had attenuated activation of DLL4, SNAIL1, DKK1 and BMP2 in response to shear stress.In conclusion endothelial cells of the patients with thoracic aortic aneurysm have dysregulated Notch, BMP and WNT/beta-catenin related signaling. Shear stress-response and cross-talk between Notch and Wnt pathways that normally ensures aortic integrity and resistance of endothelial cells to stress is impaired in aneurysmal patients. (c) 2018 Elsevier B.V. All rights reserved.
AB - Cellular and molecular mechanisms of thoracic aortic aneurysm are still not clear and therapeutic approaches are mostly absent. The role of endothelial cells in aortic wall integrity is emerging from recent studies. Although Notch pathway ensures endothelial development and integrity, and NOTCH1 mutations have been associated with thoracic aortic aneurysms, the role of this pathway in aneurysm remains elusive. The purpose of the present work was to study functions of Notch genes in endothelial cells of patients with sporadic thoracic aortic aneurysm.Aortic endothelial cells were isolated from aortic tissue of patients with thoracic aortic aneurysm and healthy donors. Gene expression of Notch and related BMP and WNT/beta-catenin pathways was estimated by qPCR; WNT/beta-catenin signaling was studied by TCF-luciferase reporter. To study the stress-response the cells were subjected to laminar shear stress and the expression of corresponding genes was estimated by qPCR.Analyses of mRNA expression of Notch genes, Notch target genes and Notch related pathways showed that endothelial cells of aneurysm patients have dysregulated Notch/BMP/WNT pathways compared to donor cells. Activity of Wnt pathway was significantly elevated in endothelial cells of the patients. Cells from patients had attenuated activation of DLL4, SNAIL1, DKK1 and BMP2 in response to shear stress.In conclusion endothelial cells of the patients with thoracic aortic aneurysm have dysregulated Notch, BMP and WNT/beta-catenin related signaling. Shear stress-response and cross-talk between Notch and Wnt pathways that normally ensures aortic integrity and resistance of endothelial cells to stress is impaired in aneurysmal patients. (c) 2018 Elsevier B.V. All rights reserved.
KW - Endothelial cells
KW - Notch
KW - Shear stress
KW - Thoracic aortic aneurysms
KW - Wnt
KW - TRANSCRIPTIONAL ACTIVATION
KW - DLL4/NOTCH1
KW - COMPLEX
KW - MECHANISMS
KW - MALFORMATIONS
KW - JAGGED1
KW - MUTATIONS
KW - WNT
KW - EXPRESSION
KW - VALVE DISEASE
UR - http://www.scopus.com/inward/record.url?scp=85053500882&partnerID=8YFLogxK
U2 - 10.1016/j.atherosclerosissup.2018.08.002
DO - 10.1016/j.atherosclerosissup.2018.08.002
M3 - Article
AN - SCOPUS:85053500882
VL - 35
SP - e6-e13
JO - Atherosclerosis Supplements
JF - Atherosclerosis Supplements
SN - 1567-5688
ER -
ID: 35805893