Open Access
Frontiers in Cardiovascular Medicine, volume 9
Crenigacestat (LY3039478) inhibits osteogenic differentiation of human valve interstitial cells from patients with aortic valve calcification in vitro
Publication type: Journal Article
Publication date: 2022-09-29
Journal:
Frontiers in Cardiovascular Medicine
Quartile SCImago
Q1
Quartile WOS
Q2
Impact factor: 3.6
ISSN: 2297055X
PubMed ID:
36247471
Cardiology and Cardiovascular Medicine
Abstract
Calcific aortic valve disease (CAVD) is one of the dangerous forms of vascular calcification. CAVD leads to calcification of the aortic valve and disturbance of blood flow. Despite high mortality, there is no targeted therapy against CAVD or vascular calcification. Osteogenic differentiation of valve interstitial cells (VICs) is one of the key factors of CAVD progression and inhibition of this process seems a fruitful target for potential therapy. By our previous study we assumed that inhibitors of Notch pathway might be effective to suppress aortic valve leaflet calcification. We tested CB-103 and crenigacestat (LY3039478), two selective inhibitors of Notch-signaling, for suppression of osteogenic differentiation of VICs isolated from patients with CAVD in vitro. Effect of inhibitors were assessed by the measurement of extracellular matrix calcification and osteogenic gene expression. For effective inhibitor (crenigacestat) we also performed MTT and proteomics study for better understanding of its effect on VICs in vitro. CB-103 did not affect osteogenic differentiation. Crenigacestat completely inhibited osteogenic differentiation (both matrix mineralization and Runx2 expression) in the dosages that had no obvious cytotoxicity. Using proteomics analysis, we found several osteogenic differentiation-related proteins associated with the effect of crenigacestat on VICs differentiation. Taking into account that crenigacestat is FDA approved for clinical trials for anti-tumor therapy, we argue that this drug could be considered as a potential inhibitor of cardiovascular calcification.
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Citations by publishers
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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Lobov A. A. et al. Crenigacestat (LY3039478) inhibits osteogenic differentiation of human valve interstitial cells from patients with aortic valve calcification in vitro // Frontiers in Cardiovascular Medicine. 2022. Vol. 9.
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Lobov A. A., Boyarskaya N. V., Kachanova O. S., Gromova E. S., Shishkova A. A., Zainullina B. R., Pishchugin A. S., Filippov A. A., Uspensky V. E., Malashicheva A. B. Crenigacestat (LY3039478) inhibits osteogenic differentiation of human valve interstitial cells from patients with aortic valve calcification in vitro // Frontiers in Cardiovascular Medicine. 2022. Vol. 9.
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TY - JOUR
DO - 10.3389/fcvm.2022.969096
UR - https://doi.org/10.3389%2Ffcvm.2022.969096
TI - Crenigacestat (LY3039478) inhibits osteogenic differentiation of human valve interstitial cells from patients with aortic valve calcification in vitro
T2 - Frontiers in Cardiovascular Medicine
AU - Lobov, Arseniy A
AU - Boyarskaya, Nadezhda V
AU - Kachanova, Olga S
AU - Gromova, Ekaterina S
AU - Shishkova, Anastassia A
AU - Zainullina, Bozhana R
AU - Pishchugin, Alexander S
AU - Filippov, Alexey A
AU - Uspensky, Vladimir E
AU - Malashicheva, Anna B
PY - 2022
DA - 2022/09/29 00:00:00
PB - Frontiers Media S.A.
VL - 9
PMID - 36247471
SN - 2297-055X
ER -
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@article{2022_Lobov,
author = {Arseniy A Lobov and Nadezhda V Boyarskaya and Olga S Kachanova and Ekaterina S Gromova and Anastassia A Shishkova and Bozhana R Zainullina and Alexander S Pishchugin and Alexey A Filippov and Vladimir E Uspensky and Anna B Malashicheva},
title = {Crenigacestat (LY3039478) inhibits osteogenic differentiation of human valve interstitial cells from patients with aortic valve calcification in vitro},
journal = {Frontiers in Cardiovascular Medicine},
year = {2022},
volume = {9},
publisher = {Frontiers Media S.A.},
month = {sep},
url = {https://doi.org/10.3389%2Ffcvm.2022.969096},
doi = {10.3389/fcvm.2022.969096}
}
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