Clinical Physiology of Circulation

ISSN 1814-6910 (Print)
ISSN 2410-9134 (Online)

 

Chief Editor

Leo A. Bockeria, MD, PhD, DSc, Professor, Academician of Russian Academy of Sciences, President of Bakoulev National Medical Research Center for Cardiovascular Surgery


Issue's catalogue ➤ КФК. 2025; 22 (2): 115-198 ➤ Ключевые внутриклеточные сигнальные пути трансдукции напряжения сдвига эндотелиальных клеток сосудистой стенки

Key intracellular signaling pathways of shear stress transduction of vascu-lar wall endothelial cells

Authors: Cygan V.N.1, Sannikov A.B.2

Company:
1 Department of Pathological Physiology by name V.V. Pashutin, St. Petersburg Military Medical Academy by name S.M. Kirov, St. Petersburg, Russian Federation
2 Department of Surgical Diseases with a course in оbstetrics and gynecology, “Privolzsky Research Medical University” (Vladimir Branch), Vladimir, Russian Federation

E-mail: Сведения доступны для зарегистрированных пользователей.

DOI: https://doi.org/10.24022/1814-6910-2025-22-2-134-149

UDC: 616.13/14:611.018.74

Link: Clinical Physiology of Blood Circulaiton. 2025; 22 (2): 134-149

Quote as: Cygan V.N., Sannikov A.B. Key intracellular signaling pathways of shear stress transduction of vascular wall endothelial cells. Clinical Physiology of Circulation. 2025; 22 (2): 134–149 (in Russ.). DOI: 10.24022/1814-6910- 2025-22-2-134-149

Keywords:  endothelial cell vascular wall shear stress mechanotransduction intracellular signaling signaling pathways

Received / Accepted:  14.05.2025 / 27.05.2025

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Abstract

This review characterizes the main intracellular transduction signaling pathways from endothelial cell shear stress mechanosensory to changes in its biochemical activity. According to modern data, the most significant transduction pathways are: Pho-RAS-RAF-MEK-MAPK/ERK, PI3K/AKT/mTOR, MEK5–ERK5–MEF2–AMPK and the Notch pathway, which got their name from cascading signaling by step-by-step activation of a large number of protein kinases with tyrosine or serine/threonine specification, as well as protein adapters in the phosphorylation of which they are directly involved. The final destinations of these transduction pathways are their participation in the regulation of intranuclear transcription, which can have a significant impact on the main biological processes, which include: the interaction of endothelial cells with their stem progenitors and their proliferation, further morphogenesis and apoptosis, embryogenesis and angiogenesis. Current evidence highlights the possibility of the cross-influence of these signaling pathways on many biological processes. Through their involvement in intercellular interaction, these transduction signaling pathways are able not only to ensure the stability of the endothelium under physiological conditions of varying shear stress, but also to trigger changes in the phenotype of the endothelial cell during the development of proinflammatory reactions associated with the migration of monocytes and other macrophages to the vascular wall, which is one of the key aspects of the development of endothelial dysfunction. Signal transduction through the highly conserved Notch pathway plays a special role in such intercellular communication, which is currently receiving increased attention. A complete understanding of the key points of various ways of mechanotransduction of signals in physiological conditions will allow us to outline new approaches in the treatment of cardiovascular diseases.

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****
  1. Lim X.R., Harraz O.F. Mechanosensing by Vascular Endothelium. Annu. Rev. Physiol. 2024; 86: 71–97. DOI: 10.1146/annurev-physiol-042022-030946
  2. Jurj A., Ionescu C., Berindan-Neagoe I., Braicu C. The extracellular matrix alteration, implication in modulation of drug resistance mechanism: friends or foes? J. Exp. Clin. Cancer Res. 2022; 41 (1): 276. DOI: 10.1186/s13046-022-02484-1
  3. Vittum Z., Cocchiaro S., Mensah S.A. Basal endothelial glycocalyx’s response to shear stress: a review of structure, function, and clinical implications. Front. Cell. Dev. Biol. 2024; 12: 1371769. DOI: 10.3389/fcell.2024.1371769
  4. Cygan V.N., Sannikov A.B. Molecular sensors of shear stress transduction of vascular wall endothelial cells. Clinical Physiology of Circulation. 2025; 22 (1): 33–46 (in Russ.). DOI: 10.24022/1814-6910-2025-22-1-33-46
  5. He L., Zhang C.L., Chen Q., Wang L., Huang Y. Endothelial shear stress signal transduction and atherogenesis: From mechanisms to therapeutics. Pharmacol. Ther. 2022; 235: 108152. DOI: 10.1016/j.pharmthera.2022.108152
  6. Nunes K.P., R.C. Webb. New insights into RhoA/Rho-kinase signaling: a key regulator of vascular contraction. Small GTPases. 2021; 12 (5– 6): 458–469. DOI: 10.1080/21541248.2020.1822721
  7. Liu Yu., Chen J., Fontes S. K., Bautista E.N., Cheng Zh. Physiological and pathological roles of protein kinase A in the heart. Cardiovasc. Res. 2021; 118 (2): 386–398. DOI: 10.1093/cvr/cvab008
  8. Hassan D., Menges C.W., Testa J.R., Bellacosa A. AKT kinases as therapeutic targets. J. Experim. Clin. Cancer Research. 2024; 43 (1): 313. DOI: 10.1186/s13046-024-03207-4
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  34. Karabiyik C., Vicinanza M., Rubinsztein D.C. Glucose starvation induces autophagy via ULK1-mediated activation of PIKfyve in an AMPK- dependent manner. Dev. Cell. 2021; 56 (13): 1961–1975. DOI: 10.1016/j.devcel.2021.05.010
  35. Giaimo B.D., Borggrefe T. Introduction to molecular mechanisms in notch signal transduction and disease pathogenesis. Adv. Exp. Med. Biol. 2018: 1066: 3–30. DOI: 10.1007/978-3-319-89512-3_1
  36. Gude N., Sussman M. Notch signaling and cardiac repair. J. Molecul. Cell. Cardiol. 2012; 52 (6): 1226–1232. DOI: 10.1016/j.yjmcc.2012.03.007
  37. Martinez Arias A., Zecchini V., Brennan K. CSL-independent Notch signaling: a checkpoint in cell fate decisions during development? Curr. Opin. Genet. Dev. 2002; 12 (5): 524–533. DOI: 10.1016/s0959-437x(02)00336-2
  38. Li D., Masiero M. The Notch Jagged1 as a target for anti-tumor therapy. Front. Oncol. 2014; 4: Article 254. DOI: 10.3389/fonc.2014.00254
  39. D’Souza B., Meloty-Kapella L., Weinmaster G. Canonical and non-canonical notch ligands. Curr. Top. Develop. Biol. 2010; 92: 73–129. DOI: 10.1016/S0070-2153(10)92003-6
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About Authors

  • Vasily N. Tsygan, Dr. Med. Sci., Professor, Academician of the Russian Academy of Natural Sciences, Head of the department of pathological physiology after V.V. Pashutin; ORCID
  • Alexander B. Sannikov, Cand. Med. Sci., Associate Professor, Angiologist, Vascular Surgeon; ORCID

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