Different Notch signaling in cells from calcified bicuspid and tricuspid aortic valves

Calcific aortic valve disease is the most common heart valve disease in the Western world. Bicuspid and tricuspid aortic valve calcifications are traditionally considered together although the dynamics of the disease progression is different between the two groups of patients. Notch signaling is cri...

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Bibliographic Details
Published in:Journal of molecular and cellular cardiology 2018-01, Vol.114, p.211-219
Main Authors: Kostina, A., Shishkova, A., Ignatieva, E., Irtyuga, O., Bogdanova, M., Levchuk, K., Golovkin, A., Zhiduleva, E., Uspenskiy, V., Moiseeva, O., Faggian, G., Vaage, J., Kostareva, A., Rutkovskiy, A., Malashicheva, A.
Format: Article
Language:English
Subjects:
Aortic Valve - metabolism
Aortic Valve - pathology
Aortic Valve Stenosis - blood
Aortic Valve Stenosis - metabolism
Biomarkers - metabolism
Calcific aortic valve disease
Calcinosis - blood
Calcinosis - metabolism
Cell Differentiation
Discriminant Analysis
Endothelial cells
Endothelial Cells - metabolism
Fibrosis
Gene Expression Regulation
Humans
Interstitial cells
Ligands
Mesoderm - metabolism
Mitral Valve - metabolism
Muscle, Smooth - metabolism
Notch
Osteoblasts - metabolism
Osteogenesis
Osteopontin - blood
Receptors, Notch - metabolism
Signal Transduction
Tricuspid Valve - metabolism
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Summary:Calcific aortic valve disease is the most common heart valve disease in the Western world. Bicuspid and tricuspid aortic valve calcifications are traditionally considered together although the dynamics of the disease progression is different between the two groups of patients. Notch signaling is critical for bicuspid valve development and NOTCH1 mutations are associated with bicuspid valve and calcification. We hypothesized that Notch-dependent mechanisms of valve mineralization might be different in the two groups. We used aortic valve interstitial cells and valve endothelial cells from patients with calcific aortic stenosis with bicuspid or tricuspid aortic valve. Expression of Notch-related genes in valve interstitial cells by qPCR was different between bicuspid and tricuspid groups. Discriminant analysis of gene expression pattern in the interstitial cells revealed that the cells from calcified bicuspid valves formed a separate group from calcified tricuspid and control cells. Interstitial cells from bicuspid calcified valves demonstrated significantly higher sensitivity to stimuli at early stages of induced proosteogenic differentiation and were significantly more sensitive to the activation of proosteogenic OPN, ALP and POSTIN expression by Notch activation. Notch-activated endothelial-to-mesenchymal transition and the corresponding expression of HEY1 and SLUG were also more prominent in bicuspid valve derived endothelial cells compared to the cells from calcified tricuspid and healthy valves. Early signaling events including Notch-dependent mechanisms that are responsible for the initiation of aortic valve calcification are different between the patients with bicuspid and tricuspid aortic valves. [Display omitted] •Initiating mechanisms of aortic valve calcification are different between patients with bicuspid and tricuspid aortic valves.•Early Notch-dependent mechanisms of calcification are different in cells of bicuspid and tricuspid aortic valves.•Interstitial cells from calcified bicuspid valves formed a separate group from calcified tricuspid and control cells by expression of Notch and proosteogenic genes.
ISSN:0022-2828
1095-8584
DOI:10.1016/j.yjmcc.2017.11.009