Endothelial cells control vascular growth via regulation of Notch signaling pathway in mesenchymal stromal cells

Beloglazova I.B.

Chazov National Medical Research Center of Cardiology

ORCID: 0000-0002-2345-3681

Zubkova E.S.

Chazov National Medical Research Center of Cardiology

ORCID: 0000-0002-0512-3670

Dergilev K.V.

Chazov National Medical Research Center of Cardiology

ORCID: 0000-0003-2712-4997

Goltseva Yu.D.

Chazov National Medical Research Center of Cardiology

ORCID: 0000-0002-6367-3785

Kruchinin S.N.

Chazov National Medical Research Center of Cardiology;
Lomonosov Moscow State University of Fine Chemical Technologies

ORCID: 0009-0006-1583-6582

Parfyonova Ye.V.

Chazov National Medical Research Center of Cardiology;
Lomonosov Moscow State University

ORCID: 0000-0002-0969-5780

Endothelial cells control vascular growth via regulation of Notch signaling pathway in mesenchymal stromal cells

Authors:

Beloglazova I.B., Zubkova E.S., Dergilev K.V., Goltseva Yu.D., Kruchinin S.N., Parfyonova Ye.V.

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Journal: Russian Cardiology Bulletin. 2024;19(2): 32‑38

DOI: 10.17116/Cardiobulletin20241902132

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To cite this article:

Beloglazova IB, Zubkova ES, Dergilev KV, Goltseva YuD, Kruchinin SN, Parfyonova YeV. Endothelial cells control vascular growth via regulation of Notch signaling pathway in mesenchymal stromal cells. Russian Cardiology Bulletin. 2024;19(2):32‑38. (In Russ.)
https://doi.org/10.17116/Cardiobulletin20241902132

Подписка 2025 (Russian Cardiology Bulletin)

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BACKGROUND

The Notch signaling pathway is essential in embryogenesis of heart and postnatal functioning and remodeling of vascular network. In addition to canonical Notch signaling, there is non-canonical signaling pathway including interactions with elements of extracellular matrix. Multifactorial nature of Notch signaling pathway supposes that its exact mechanism is unclear.

OBJECTIVE

To study the role of Notch signaling pathway in communication of endothelial and mesenchymal stromal cells (MSCs) in angiogenesis before extracellular matrix assembly (19 hours) to exclude the influence of non-canonical signaling system.

MATERIAL AND METHODS

We used a model of capillary-like network formation by human umbilical vein endothelial cells (HUVECs) on Matrigel. Analysis of gene expression during co-culture of MSCs and HUVECs was performed using real-time PCR.

RESULTS

Γ-Secretase inhibitor, which blocks Notch activation, suppressed capillary-like HUVECs network formation on Matrigel by more than 2.5 fold and blocked expression of some Notch-dependent genes in the 2D model of capillary-like network formation in the co-culture of MSCs and HUVECs. In MSCs, the Notch signaling pathway is essential in regulation of expression of genes JAG1, Notch1, Notch3, HES1, HEY1, EFNB2, ANGPT2, TGFB3, ITGB3, SDC2, in endothelial cells — Notch4, HES2. Changes in expression of Notch-dependent genes HES and HEY in MSCs during co-culture were significantly higher than in HUVECs.

CONCLUSION

HUVECs drive the switch of MSCs to a pro-angiogenic phenotype through Notch signaling pathway. Our findings indicate the prospect of a method for modulating angiogenesis processes using cellular therapeutics based on MSCs with constitutively active Notch signaling.

Keywords:

co-culture

angiogenesis

MSC

HUVEC

Notch

γ-secretase

ephrins

syndecan-2

angiopoietin-2

Matrigel

Authors:

Beloglazova I.B.

Chazov National Medical Research Center of Cardiology

ORCID: 0000-0002-2345-3681

Zubkova E.S.

Chazov National Medical Research Center of Cardiology

ORCID: 0000-0002-0512-3670

Dergilev K.V.

Chazov National Medical Research Center of Cardiology

ORCID: 0000-0003-2712-4997

Goltseva Yu.D.

Chazov National Medical Research Center of Cardiology

ORCID: 0000-0002-6367-3785

Kruchinin S.N.

Chazov National Medical Research Center of Cardiology;
Lomonosov Moscow State University of Fine Chemical Technologies

ORCID: 0009-0006-1583-6582

Parfyonova Ye.V.

Chazov National Medical Research Center of Cardiology;
Lomonosov Moscow State University

ORCID: 0000-0002-0969-5780

Received:

12.11.2023

Accepted:

23.11.2023

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