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 (1): 1-114 ➤ Молекулярные сенсоры трансдукции напряжения сдвига эндотелиальных клеток сосудистой стенки

Molecular sensors of shear stress transduction of vascular 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 Clinic «MedСi», Vladimir, Russian Federation

E-mail: Сведения доступны для зарегистрированных пользователей.

DOI: https://doi.org/10.24022/1814-6910-2025-22-1-33-46

UDC: 616.13/14:611.018.74

Link: Clinical Physiology of Blood Circulaiton. 2025; 22 (1): 33-46

Quote as: 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

Keywords:  endothelial cell vascular wall mechanotransduction mechanosensors extracellular matrix glycocalyx αVß3-integrins connexons ion channels PIEZO1 intracellular signal transmission

Received / Accepted:  02.02.2025 / 19.02.2025

Full text:
Subscribe 🔒

Abstract

Further study of various aspects of the biology of endothelial cells (ECs) remains an urgent task of scientific research, as it underlies not only rheological hemostasis in physiological conditions, but is also the key to understanding the mechanisms of development of almost all cardiovascular diseases. One of the main factors that can significantly affect the functional state of the vascular wall endothelium under hemodynamic conditions is a change in shear Stress (SS). The process of changing the biochemical activity of ECs under the influence of this mechanical factor, from the point of view of biophysics, is called mechanotransduction. For the perception of mechanical signals that initiate a further intracellular cascade of events up to transcriptional changes, the ECs must have mechanisms with sensory abilities on its surface. According to modern data, a large number of protein molecules localized in the extracellular matrix (ECM), glycocalyx (GCX) and plasma membrane (PM) are considered as primary mechanosensors. Among the main such proteins are: fibronectin; glycosaminoglycans syndecan and glypican; hyaloderin CD44 and hyaluronan; αVß3- integrins, which are part of adhesives; connexons; mechanosensitive ion channels PIEZO1 and a large number of protein kinases, the cascading activation of which, upon receiving a signal from outside the cell, forms the basis of two main signaling pathways for further intracellular transmission: Ras/Raf/MEK/ERK and PI3K/AKT/mTOR. The review presents material summarizing current data on the molecular structure and degree of involvement of various protein molecules of endothelial cells as primary sensors of the mechanical signal and its further intracellular transduction.

References

  1. Zhou J., Yi-Shuan L., Chien Sh. Shear sfress – initiated signaling and its regulation of endothelial function. arterioscler, Tromb. Vasc. Biol. 2014; 34 (10): 2191–2198. DOI: 0.1161/atvbaha.114.303422
  2. Cheng H., Zhong W., Wang L., Zhang Q., Mae Xi., Wang Y. et al. Effects of shear stress on vascular endothelial functions in atherosclerosis and potential therapeutic approaches. Biomedi. Pharmacother. 2023; 158: 114198. DOI: 10.1016/j.biopha.2022.114198
  3. Bonnans C., Chou J., Werb Z. Remodelling the extracellular matrix in development and disease. Nat. Rev. Mol. Cell Biol. 2014; 15 (12): 786–801. DOI: 10.1038/nrm3904
  4. Munci J.M., Weave V.M. The physical and biochemical properties of the extracellular matrix regulate cell fate. Curr. Top. Dev. Biol. 2018; 13: 1–37. DOI: 10.1016/bs.ctdb.2018.02.002
  5. Walker C., Mojares E., Hernández A Del Río. Role of extracellular matrix in development and cancer progression. Int. J. Mol. Sci. 2018; 19 (10): 3028. DOI: 10.3390/ijms19103028
  6. Taha I.N., Naba A. Exploring the extracellular matrix in health and disease using proteomics. Essays Biochem. 2019; 6: 417–432. DOI: 10.1042/EBC20190001
  7. Dalton C.J., Lemmon Ch.A. Fibronectin: molecular structure, fibrillar structure and mechanochemical signaling. Cell. 2021; 10: 2443. DOI: 10.3390/cells10092443
  8. Chignalia A.Z., Yetimakman F., Christiaans S.C., Unal S., Bayrakci B., Wagener B.M. et al. The glycocalyx and trauma: a review. Shock. 2016; 45: 338–348. DOI: 10.1097/SHK.0000000000000513
  9. Harding I.C., Mitra R., Mensah S.A., Nersesyan A., Bal N.N., Ebong E.E. Endothelial barrier reinforcement relies on flow-regulated glycocalyx, a potential therapeutic target. Biorheology. 2019; 56: 131–149. DOI: 10.3233/BIR-180205
  10. Butler M.J., Down C.J., Foster R.R., Satchell S.C. The pathological relevance of increased endothelial glycocalyx permeability. Am. J. Pathol. 2020; 190: 742–751. DOI: 10.1016/j.ajpath.2019.11.015
  11. Zhu J., Li X., Yin J., Hu Y., Gu Y., Pan S. Glycocalyx degradation leads to blood-brain barrier dysfunction and brain edema after asphyxia cardiac arrest in rats. J. Cereb. Blood Flow Metab. 2018; 38: 1979–1992. DOI: 10.1177/0271678X17726062
  12. De Ore B.J., Partyka P.P., Fan F., Galie P.A. CD44 regulates blood-brain barrier integrity in response to fluid shear stress. BioRxiv. 2020; 3: 1–9. DOI: 10.1101/2020.01.28.924043
  13. Mohammed A.S.A., Naveed M., Jost N. Polysaccharides; classification, chemical properties, and future perspective applications in fields of pharmacology and biological medicine (a review of current applications and upcoming potentialities). J. Polym. Environ. 2021; 29: 2359–2371. DOI: 10.1007/s10924-021-02052-2
  14. Karbownik M.S., Nowak J.Z. Hyaluronan: Towards novel anti-cancer therapeutics. Pharmacol. Rep. 2013; 65 (5): 105–1074. DOI: 10.1016/s1734-1140(13)71465-8
  15. Curry F.E., Adamson R.H. Endothelial glycocalyx: Permeability barrier and mechanosensor. Ann. Biomed.Eng. 2012; 40: 828–839. DOI: 10.1007/s10439-011-0429-8
  16. Martinez-Lopez N., Singh R. Shear stress turns on the primary cilium and lipophagy. Nat. Cell Biol. 2020; 22 (9): 1029–1030. DOI: 10.1038/s41556-020-0571-3
  17. Wang Z.M., Gao X.F., Zhang J.J., Chen S.L. Primary cilia and atherosclerosis. Front. Physiol. 2021; 12: 640774. DOI: 10.3389/ fphys.2021.640774
  18. Arnaut M.A., Mahalingam B., Xiong J.P. Integrin structure, allostery and bidirectional signaling. Ann. Rev. Cell. Dev. Biol. 2005; 21: 381–410. DOI: 10.1146/annurev.cellbio.21.090704.151217
  19. Al-Yafeai Z., Person Br.H., Peretik Jo.M., Cockerham El.D., Reeves K.A. et al. Integrin affinity modulation critically regulates atherogenic endothelial activation in vitro and in vivo. Matrix Biology. 2021; 96: 87–103. DOI: 10.1016/j.matbio.2020.10.006
  20. Xiong J.P., Stehle T., Diefenbach B, Zhang R., Dunker R., Scott D.L. et al. Crystal structure of the extracellular segment of integrin αvβ3. Science. 2001; 294: 339–345. DOI: 10.1126/science.1064535
  21. Takada Y., Ye X., Simon S. The integrins. Genome Biology.2007; 8: 215. DOI: 10.1186/gb-2007-8-5-215
  22. Mc Cleverty Cl. J., Lin Di. C., Liddington R. C. Structure of the PTB domain of tensin1 and a model for its recruitment to fibrillar adhesions. Protein Sci. 2007; 16 (6): 1223–1229. DOI: 10.1110/ps.072798707
  23. Pendosa Nunes K., Webb R.C. 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
  24. McCubrey J.A., Steelman L S., Chappell W.H., Abrams S.L., Montalto G., Cervello M. et al. Mutations and deregulation of Ras/Raf/ MEK/ERK and PI3K/PTEN/Akt/mTOR cascades which alter therapy response. Oncotarget. 2012; 3 (9): 954–987. DOI: 10.18632/oncotarget.652
  25. Vitali T., Girald-Berlingeri S., Randazzo P.A., Chen P.W. Arf GAPs: A family of proteins with disparate functions that converge on a common structure, the integrin adhesion complex. Small GTPases. 2019; 10 (4): 280–288. DOI: 10.1080/21541248.2017.1299271
  26. Pearson M.A., Reczek D., Bretscher A., Karplus P.A. Structure of the ERM protein moesin reveals the FERM domain fold masked by an extended actin binding tail domain. Cell. 2000; 101 (3): 259–270. DOI: 10.1016/s0092-8674(00)80836-3
  27. Kelly D.F., Taylor D.W., Bakolitsa C., Bobkov A.A., Bankston L., Liddington R.C., Taylor K.A. Structureof the alpha-actinin-vinculin head domain complex determined by cryo-electron microscopy. J. Mol. Biol. 2006; 357: 562–573. DOI: 10.1016/j.jmb.2005.12.076
  28. Tadokoro S., Shattil S.J., Eto K., Tai V., Liddington R.C., dePereda J.M. et al. Talin binding to integrin beta tails: a final common step in integrin activation. Science. 2003; 302: 103–106. DOI: 10.1126/science.1086652
  29. Case L.B., Waterman C.M. Integration of actin dynamics and cell adhesion by a three-dimensional, mechanosensitive molecular clutch. Nat. Cell. Biol. 2015; 17: 955–963. DOI: 10.1038/ncb3191
  30. Missirlis D., Haraszti T., Scheele C.C., Wiegand T., Diaz C., Neubauez S. et al. Substrate engagement of integrins α5β1 and αvβ3 is necessary, but not sufficient, for high directional persistence in migration on fibronectin. Sci. Rep. 2016; 6: 23258. DOI: 10.1038/ srep23258
  31. Goult B.T. Zacharchenko Th., Bate N., Tsang R., Hey F., Gingras A.R. et al. RIAM and vinculin binding to talin are mutually exclusive and regulate adhesion assembly and turnover. J. Biol. Chem. 2013; 288: 8238–8249. DOI: 10.1074/jbc.M112.438119
  32. Schmidt E.P., Kuiebler W.M., Lee W.L., Downey G.P. Adhesion molecules: Master controllers of the circulatory system. Compr. Physiol. 2016; 6 (2): 945–973. DOI: 10.1002/cphy.c150020
  33. He L., Zhang C.L., Chen Q., Wang L., Huang Y. Endothelial shear stress signaltransduction and atherogenesis: From mechanisms to therapeutics. Pharmacol. Ther. 2022; 235: 108152. DOI: 10.1016/j.pharmthera.2022.108152
  34. Cheung G., Chever O., Rouach N. Connexons and Pannexons: Newcomers in neurophysiology. Fron. Cell. Neurosci. 2014; 8: 348. DOI: 10.3389/fncel.2014.00348
  35. Thevenin A.F. Proteins and mechanisms regulating gap-junction assembly, internalization, and degradation. Physiol. (Bethesda). 2013; 28 (2): 93–116. DOI: 10.1152/physiol.00038.2012
  36. Pfenniger A., Meens M.J., Pedrigi R.M., Foglia B., Sutter E., Pelli G. et al. Shear stress-induced atherosclerotic plaque composition in ApoE(-/-) mice is modulated by connexin37. Atherosclerosis. 2015; 243 (1): 1–10. DOI: 10.1016/j.atherosclerosis.2015.08.029
  37. Qu K., Wang C., Huang L., Qin X., Zhang K., Zhong Y. et al. TET-1s deficiency exacerbates oscillatory shear flow-induced atherosclerosis. Int. J. Biol. Sci. 2022; 18 (5): 2163–2180. DOI: 10.7150/ijbs.69281
  38. Xie X., Wang F., Zhu L., Yang H., Pan D., Liu Y. et al. Low shear stress induces endothelial cell apoptosis and monocyte adhesion by upregulating PECAM-1 expression. Mol. Med. Rep. 2020; 21 (6): 2580–2588. DOI: 10.3892/mmr.2020.11060
  39. Zhou J., Li Yi-Shuan, Chen Shu. Shear stress-initiated signaling and its regulation of endothelial function. Arterioscler. Thromb. Vasc. Biol. 2014; 34: 2191–2198. DOI: 10.1161/ATVBAHA.114.303422
  40. Baratchi S., Khoshmanesh K., Woodman O.L., Potocnik S., Karlheinz P., Mcityre P. Molecular sensors of blood flow in endothelial cells. Trends. Mol. Med. 2017; 23 (9): 850–868. DOI: 10.1016/j.molmed.2017.07.007
  41. Hao J., Padilla F., Dandonneau M., Lavebratt C., Lesage F., Noël J., et al. Kv1.1channels act as mechanical brake in the senses of touch and pain. Neuron. 2013; 77 (5): 899–914. DOI: 10.1016/j.neuron.2012.12.035
  42. Zhao H., Sokabe M. Tuning the mechanosensitivity of a BK channel bychanging the linker length. Cell Res. 2008; 18 (8): 871–878. DOI: 10.1038/cr.2008.88
  43. Arnadóttir J., O’Hagan R., Chen Y., Goodman M.B., Chalfie M. The DEG/ENaC protein MEC-10 regulates the transduction channel complexin Caenorhabditis elegans touch receptor neurons. J. Neurosci. 2011; 31 (35): 12695–12704. DOI: 10.1523/ JNEUROSCI.4580-10.2011
  44. Coste B., Mathur J., Schmidt M., Earley T.J., Ranade S., Petrus M.J., et al. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science. 2010; 330: 55–60. DOI: 10.1126/science.1193270
  45. Wang S., Chennupati R., Kaur H., Iring A., Wettschureck N., Offermanns S. Endothelial cation channel PIEZO1 controls blood pressure by mediating flow-induced ATP release, J. Clin. Investig. 2016; 126 (12): 4527–4536. DOI: 10.1172/JCI87343
  46. Zhao Q., Zhou H., Chi S., Wang Y., Wang J., Geng J., et al. Structure and mechanogating mechanism of the Piezo1 channel. Nature. 2018; 554 (7693): 487–492. DOI: 10.1038/nature25743
  47. Xiang-Zhi Fang, Ting Zhou, Ji-Qian Xu, Ya-Xin Wang, Miao-Miao Sun et al. Structure, kinetic properties and biological function of mechanosensitive Piezo channels. Cell Biosci. 2021; 11: 13. DOI: 10.1186/s13578-020-00522-z
  48. Ge J., Li W., Zhao Q., Li N., Chen M., Zhi P., et al. Architecture of the mammalian mechanosensitive Piezo1 channel. Nature. 2015; 527 (7576): 64–69. DOI: 10.1038/nature15247
  49. Jiang Y., Yang X., Jiang J., Xiao B. Structural designs and mechanogating mechanisms of the mechanosensitive Piezo channels. Trends Biochem. Sci. 2021; 46 (6): 472–488. DOI: 10.1016/j.tibs.2021.01.008
  50. Gaub B.M., Müller D.J. Mechanical stimulation of Piezo1 receptors depends on extracellular matrix proteins and directionality of force. Nano Lett. 2017; 17 (3): 2064–2072. DOI: 10.1021/acs.nanolett.7b00177
  51. Chen L., Qu H., Liu B., et al. Low or oscillatory shear stress and endothelial permeability in atherosclerosis. Front. Physiol. 2024; 15: 1432719. DOI: 10.3389/fphys.2024.1432719
  52. 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
  53. 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
  54. Lim X.R., Harraz O.F. Mechanosensing by vascular endothelium. Annu. Rev. Physiol. 2024; 86: 71–97. DOI: 10.1146/annurev- physiol-042022-030946
  55. Lewis A.H., Cronin M.E., Grandl J. Piezo1 ion channels are capable of conformational signaling. Neuron. 2024; 112 (18): 3161–3175. e5. DOI: 10.1016/j.neuron.2024.06.024
  56. Mokhfi F.Z., Amin M.A., Zehravi M., Sweilam Sh.H., Arjun U.V.N.V., Gupta J.K. et al. Alkaliod-based modulators of the PI3K/Akt/ mTOR pathway for cancer therapy: Understandings from pharmacological point of view. Chem. Biol. Interact. 2024; 402: 111218. DOI: 10.1016/j.cbi.2024.111218
  57. Singh A.P., Sharma A.K., Singh Th.G. Unlocking the therapeutic potential: exploring NF-kB as a viable target for diverse pharmacological approaches. Int. J. Pharmacol. Pharmaceuti. Sci. 2024; 16 (6): 1–9. DOI: 10.22159/ijpps.2024v16i6.49530
  58. Power G., Ferreira-Santos L., Martinez-Lemus L.A., Padilla J. Integrating molecular and cellular components of endothelial shear stress mechanotransduction. Am. J. Physiol. Heart Circ. Physiol. 2024; 327 (4): H989-H1003. DOI: 10.1152/ajpheart.00431.2024
  59. Solano A.S., Lavanderos B., Metwally E., Earley S. Transient receptor potential channels in vascular mechanotransduction. Am. J. Hypertens. 2025; 38 (3): 151–160. DOI: 10.1093/ajh/hpae134
  60. Jakubowski H., Witucki Ł. Homocysteine metabolites, endothelial dysfunction, and cardiovascular disease. Int. J. Mol. Sci. 2025; 26(2): 746. DOI: 10.3390/ijms26020746
****
  1. Zhou J., Yi-Shuan L., Chien Sh. Shear sfress – initiated signaling and its regulation of endothelial function. arterioscler, Tromb. Vasc. Biol. 2014; 34 (10): 2191–2198. DOI: 0.1161/atvbaha.114.303422
  2. Cheng H., Zhong W., Wang L., Zhang Q., Mae Xi., Wang Y. et al. Effects of shear stress on vascular endothelial functions in atherosclerosis and potential therapeutic approaches. Biomedi. Pharmacother. 2023; 158: 114198. DOI: 10.1016/j.biopha.2022.114198
  3. Bonnans C., Chou J., Werb Z. Remodelling the extracellular matrix in development and disease. Nat. Rev. Mol. Cell Biol. 2014; 15 (12): 786–801. DOI: 10.1038/nrm3904
  4. Munci J.M., Weave V.M. The physical and biochemical properties of the extracellular matrix regulate cell fate. Curr. Top. Dev. Biol. 2018; 13: 1–37. DOI: 10.1016/bs.ctdb.2018.02.002
  5. Walker C., Mojares E., Hernández A Del Río. Role of extracellular matrix in development and cancer progression. Int. J. Mol. Sci. 2018; 19 (10): 3028. DOI: 10.3390/ijms19103028
  6. Taha I.N., Naba A. Exploring the extracellular matrix in health and disease using proteomics. Essays Biochem. 2019; 6: 417–432. DOI: 10.1042/EBC20190001
  7. Dalton C.J., Lemmon Ch.A. Fibronectin: molecular structure, fibrillar structure and mechanochemical signaling. Cell. 2021; 10: 2443. DOI: 10.3390/cells10092443
  8. Chignalia A.Z., Yetimakman F., Christiaans S.C., Unal S., Bayrakci B., Wagener B.M. et al. The glycocalyx and trauma: a review. Shock. 2016; 45: 338–348. DOI: 10.1097/SHK.0000000000000513
  9. Harding I.C., Mitra R., Mensah S.A., Nersesyan A., Bal N.N., Ebong E.E. Endothelial barrier reinforcement relies on flow-regulated glycocalyx, a potential therapeutic target. Biorheology. 2019; 56: 131–149. DOI: 10.3233/BIR-180205
  10. Butler M.J., Down C.J., Foster R.R., Satchell S.C. The pathological relevance of increased endothelial glycocalyx permeability. Am. J. Pathol. 2020; 190: 742–751. DOI: 10.1016/j.ajpath.2019.11.015
  11. Zhu J., Li X., Yin J., Hu Y., Gu Y., Pan S. Glycocalyx degradation leads to blood-brain barrier dysfunction and brain edema after asphyxia cardiac arrest in rats. J. Cereb. Blood Flow Metab. 2018; 38: 1979–1992. DOI: 10.1177/0271678X17726062
  12. De Ore B.J., Partyka P.P., Fan F., Galie P.A. CD44 regulates blood-brain barrier integrity in response to fluid shear stress. BioRxiv. 2020; 3: 1–9. DOI: 10.1101/2020.01.28.924043
  13. Mohammed A.S.A., Naveed M., Jost N. Polysaccharides; classification, chemical properties, and future perspective applications in fields of pharmacology and biological medicine (a review of current applications and upcoming potentialities). J. Polym. Environ. 2021; 29: 2359–2371. DOI: 10.1007/s10924-021-02052-2
  14. Karbownik M.S., Nowak J.Z. Hyaluronan: Towards novel anti-cancer therapeutics. Pharmacol. Rep. 2013; 65 (5): 105–1074. DOI: 10.1016/s1734-1140(13)71465-8
  15. Curry F.E., Adamson R.H. Endothelial glycocalyx: Permeability barrier and mechanosensor. Ann. Biomed.Eng. 2012; 40: 828–839. DOI: 10.1007/s10439-011-0429-8
  16. Martinez-Lopez N., Singh R. Shear stress turns on the primary cilium and lipophagy. Nat. Cell Biol. 2020; 22 (9): 1029–1030. DOI: 10.1038/s41556-020-0571-3
  17. Wang Z.M., Gao X.F., Zhang J.J., Chen S.L. Primary cilia and atherosclerosis. Front. Physiol. 2021; 12: 640774. DOI: 10.3389/ fphys.2021.640774
  18. Arnaut M.A., Mahalingam B., Xiong J.P. Integrin structure, allostery and bidirectional signaling. Ann. Rev. Cell. Dev. Biol. 2005; 21: 381–410. DOI: 10.1146/annurev.cellbio.21.090704.151217
  19. Al-Yafeai Z., Person Br.H., Peretik Jo.M., Cockerham El.D., Reeves K.A. et al. Integrin affinity modulation critically regulates atherogenic endothelial activation in vitro and in vivo. Matrix Biology. 2021; 96: 87–103. DOI: 10.1016/j.matbio.2020.10.006
  20. Xiong J.P., Stehle T., Diefenbach B, Zhang R., Dunker R., Scott D.L. et al. Crystal structure of the extracellular segment of integrin αvβ3. Science. 2001; 294: 339–345. DOI: 10.1126/science.1064535
  21. Takada Y., Ye X., Simon S. The integrins. Genome Biology.2007; 8: 215. DOI: 10.1186/gb-2007-8-5-215
  22. Mc Cleverty Cl. J., Lin Di. C., Liddington R. C. Structure of the PTB domain of tensin1 and a model for its recruitment to fibrillar adhesions. Protein Sci. 2007; 16 (6): 1223–1229. DOI: 10.1110/ps.072798707
  23. Pendosa Nunes K., Webb R.C. 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
  24. McCubrey J.A., Steelman L S., Chappell W.H., Abrams S.L., Montalto G., Cervello M. et al. Mutations and deregulation of Ras/Raf/ MEK/ERK and PI3K/PTEN/Akt/mTOR cascades which alter therapy response. Oncotarget. 2012; 3 (9): 954–987. DOI: 10.18632/oncotarget.652
  25. Vitali T., Girald-Berlingeri S., Randazzo P.A., Chen P.W. Arf GAPs: A family of proteins with disparate functions that converge on a common structure, the integrin adhesion complex. Small GTPases. 2019; 10 (4): 280–288. DOI: 10.1080/21541248.2017.1299271
  26. Pearson M.A., Reczek D., Bretscher A., Karplus P.A. Structure of the ERM protein moesin reveals the FERM domain fold masked by an extended actin binding tail domain. Cell. 2000; 101 (3): 259–270. DOI: 10.1016/s0092-8674(00)80836-3
  27. Kelly D.F., Taylor D.W., Bakolitsa C., Bobkov A.A., Bankston L., Liddington R.C., Taylor K.A. Structureof the alpha-actinin-vinculin head domain complex determined by cryo-electron microscopy. J. Mol. Biol. 2006; 357: 562–573. DOI: 10.1016/j.jmb.2005.12.076
  28. Tadokoro S., Shattil S.J., Eto K., Tai V., Liddington R.C., dePereda J.M. et al. Talin binding to integrin beta tails: a final common step in integrin activation. Science. 2003; 302: 103–106. DOI: 10.1126/science.1086652
  29. Case L.B., Waterman C.M. Integration of actin dynamics and cell adhesion by a three-dimensional, mechanosensitive molecular clutch. Nat. Cell. Biol. 2015; 17: 955–963. DOI: 10.1038/ncb3191
  30. Missirlis D., Haraszti T., Scheele C.C., Wiegand T., Diaz C., Neubauez S. et al. Substrate engagement of integrins α5β1 and αvβ3 is necessary, but not sufficient, for high directional persistence in migration on fibronectin. Sci. Rep. 2016; 6: 23258. DOI: 10.1038/ srep23258
  31. Goult B.T. Zacharchenko Th., Bate N., Tsang R., Hey F., Gingras A.R. et al. RIAM and vinculin binding to talin are mutually exclusive and regulate adhesion assembly and turnover. J. Biol. Chem. 2013; 288: 8238–8249. DOI: 10.1074/jbc.M112.438119
  32. Schmidt E.P., Kuiebler W.M., Lee W.L., Downey G.P. Adhesion molecules: Master controllers of the circulatory system. Compr. Physiol. 2016; 6 (2): 945–973. DOI: 10.1002/cphy.c150020
  33. He L., Zhang C.L., Chen Q., Wang L., Huang Y. Endothelial shear stress signaltransduction and atherogenesis: From mechanisms to therapeutics. Pharmacol. Ther. 2022; 235: 108152. DOI: 10.1016/j.pharmthera.2022.108152
  34. Cheung G., Chever O., Rouach N. Connexons and Pannexons: Newcomers in neurophysiology. Fron. Cell. Neurosci. 2014; 8: 348. DOI: 10.3389/fncel.2014.00348
  35. Thevenin A.F. Proteins and mechanisms regulating gap-junction assembly, internalization, and degradation. Physiol. (Bethesda). 2013; 28 (2): 93–116. DOI: 10.1152/physiol.00038.2012
  36. Pfenniger A., Meens M.J., Pedrigi R.M., Foglia B., Sutter E., Pelli G. et al. Shear stress-induced atherosclerotic plaque composition in ApoE(-/-) mice is modulated by connexin37. Atherosclerosis. 2015; 243 (1): 1–10. DOI: 10.1016/j.atherosclerosis.2015.08.029
  37. Qu K., Wang C., Huang L., Qin X., Zhang K., Zhong Y. et al. TET-1s deficiency exacerbates oscillatory shear flow-induced atherosclerosis. Int. J. Biol. Sci. 2022; 18 (5): 2163–2180. DOI: 10.7150/ijbs.69281
  38. Xie X., Wang F., Zhu L., Yang H., Pan D., Liu Y. et al. Low shear stress induces endothelial cell apoptosis and monocyte adhesion by upregulating PECAM-1 expression. Mol. Med. Rep. 2020; 21 (6): 2580–2588. DOI: 10.3892/mmr.2020.11060
  39. Zhou J., Li Yi-Shuan, Chen Shu. Shear stress-initiated signaling and its regulation of endothelial function. Arterioscler. Thromb. Vasc. Biol. 2014; 34: 2191–2198. DOI: 10.1161/ATVBAHA.114.303422
  40. Baratchi S., Khoshmanesh K., Woodman O.L., Potocnik S., Karlheinz P., Mcityre P. Molecular sensors of blood flow in endothelial cells. Trends. Mol. Med. 2017; 23 (9): 850–868. DOI: 10.1016/j.molmed.2017.07.007
  41. Hao J., Padilla F., Dandonneau M., Lavebratt C., Lesage F., Noël J., et al. Kv1.1channels act as mechanical brake in the senses of touch and pain. Neuron. 2013; 77 (5): 899–914. DOI: 10.1016/j.neuron.2012.12.035
  42. Zhao H., Sokabe M. Tuning the mechanosensitivity of a BK channel bychanging the linker length. Cell Res. 2008; 18 (8): 871–878. DOI: 10.1038/cr.2008.88
  43. Arnadóttir J., O’Hagan R., Chen Y., Goodman M.B., Chalfie M. The DEG/ENaC protein MEC-10 regulates the transduction channel complexin Caenorhabditis elegans touch receptor neurons. J. Neurosci. 2011; 31 (35): 12695–12704. DOI: 10.1523/ JNEUROSCI.4580-10.2011
  44. Coste B., Mathur J., Schmidt M., Earley T.J., Ranade S., Petrus M.J., et al. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science. 2010; 330: 55–60. DOI: 10.1126/science.1193270
  45. Wang S., Chennupati R., Kaur H., Iring A., Wettschureck N., Offermanns S. Endothelial cation channel PIEZO1 controls blood pressure by mediating flow-induced ATP release, J. Clin. Investig. 2016; 126 (12): 4527–4536. DOI: 10.1172/JCI87343
  46. Zhao Q., Zhou H., Chi S., Wang Y., Wang J., Geng J., et al. Structure and mechanogating mechanism of the Piezo1 channel. Nature. 2018; 554 (7693): 487–492. DOI: 10.1038/nature25743
  47. Xiang-Zhi Fang, Ting Zhou, Ji-Qian Xu, Ya-Xin Wang, Miao-Miao Sun et al. Structure, kinetic properties and biological function of mechanosensitive Piezo channels. Cell Biosci. 2021; 11: 13. DOI: 10.1186/s13578-020-00522-z
  48. Ge J., Li W., Zhao Q., Li N., Chen M., Zhi P., et al. Architecture of the mammalian mechanosensitive Piezo1 channel. Nature. 2015; 527 (7576): 64–69. DOI: 10.1038/nature15247
  49. Jiang Y., Yang X., Jiang J., Xiao B. Structural designs and mechanogating mechanisms of the mechanosensitive Piezo channels. Trends Biochem. Sci. 2021; 46 (6): 472–488. DOI: 10.1016/j.tibs.2021.01.008
  50. Gaub B.M., Müller D.J. Mechanical stimulation of Piezo1 receptors depends on extracellular matrix proteins and directionality of force. Nano Lett. 2017; 17 (3): 2064–2072. DOI: 10.1021/acs.nanolett.7b00177
  51. Chen L., Qu H., Liu B., et al. Low or oscillatory shear stress and endothelial permeability in atherosclerosis. Front. Physiol. 2024; 15: 1432719. DOI: 10.3389/fphys.2024.1432719
  52. 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
  53. 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
  54. Lim X.R., Harraz O.F. Mechanosensing by vascular endothelium. Annu. Rev. Physiol. 2024; 86: 71–97. DOI: 10.1146/annurev- physiol-042022-030946
  55. Lewis A.H., Cronin M.E., Grandl J. Piezo1 ion channels are capable of conformational signaling. Neuron. 2024; 112 (18): 3161–3175. e5. DOI: 10.1016/j.neuron.2024.06.024
  56. Mokhfi F.Z., Amin M.A., Zehravi M., Sweilam Sh.H., Arjun U.V.N.V., Gupta J.K. et al. Alkaliod-based modulators of the PI3K/Akt/ mTOR pathway for cancer therapy: Understandings from pharmacological point of view. Chem. Biol. Interact. 2024; 402: 111218. DOI: 10.1016/j.cbi.2024.111218
  57. Singh A.P., Sharma A.K., Singh Th.G. Unlocking the therapeutic potential: exploring NF-kB as a viable target for diverse pharmacological approaches. Int. J. Pharmacol. Pharmaceuti. Sci. 2024; 16 (6): 1–9. DOI: 10.22159/ijpps.2024v16i6.49530
  58. Power G., Ferreira-Santos L., Martinez-Lemus L.A., Padilla J. Integrating molecular and cellular components of endothelial shear stress mechanotransduction. Am. J. Physiol. Heart Circ. Physiol. 2024; 327 (4): H989-H1003. DOI: 10.1152/ajpheart.00431.2024
  59. Solano A.S., Lavanderos B., Metwally E., Earley S. Transient receptor potential channels in vascular mechanotransduction. Am. J. Hypertens. 2025; 38 (3): 151–160. DOI: 10.1093/ajh/hpae134
  60. Jakubowski H., Witucki Ł. Homocysteine metabolites, endothelial dysfunction, and cardiovascular disease. Int. J. Mol. Sci. 2025; 26(2): 746. DOI: 10.3390/ijms26020746

About Authors

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

 If you found mistakes, select text and press Alt+A