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

A. Kostina, A. Shishkova, E. Ignatieva, O. Irtyuga, M. Bogdanova, K. Levchuk, A. Golovkin, E. Zhiduleva, V. Uspenskiy, O. Moiseeva, G. Faggian, J. Vaage, A. Kostareva, A. Rutkovskiy, A. Malashicheva

Результат исследований: Научные публикации в периодических изданияхстатья

10 Цитирования (Scopus)

Аннотация

Aims 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. Methods and results 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. Conclusion 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.

Язык оригиналаанглийский
Страницы (с-по)211-219
Число страниц9
ЖурналJournal of Molecular and Cellular Cardiology
Том114
DOI
СостояниеОпубликовано - 1 янв 2018

Предметные области Scopus

  • Кардиология и сердечно-сосудистая медицина
  • Молекулярная биология

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  • Цитировать

    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. (2018). Different Notch signaling in cells from calcified bicuspid and tricuspid aortic valves. Journal of Molecular and Cellular Cardiology, 114, 211-219. https://doi.org/10.1016/j.yjmcc.2017.11.009