Научно-практический журнал
«Клиническая физиология кровообращения»

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

 

Главный редактор

Лео Антонович Бокерия, доктор медицинских наук, профессор, академик РАН и РАМН, президент ФГБУ «НМИЦ ССХ им. А.Н. Бакулева» МЗ РФ


Каталог статей ➤ КФК. 2025; 22 (1): 1-114 ➤ Молекулярные сенсоры трансдукции напряжения сдвига эндотелиальных клеток сосудистой стенки

Молекулярные сенсоры трансдукции напряжения сдвига эндотелиальных клеток сосудистой стенки

Авторы: Цыган В.Н.1, Санников А.Б.2

Организация:
1 Кафедра патологической физиологии им. В.В. Пашутина Санкт-Петербургской Военно-медицинской академии им. С.М. Кирова, Санкт-Петербург, Российская Федерация
2 Клиника «МедСи», Владимир, Российская Федерация

Для корреспонденции: Сведения доступны для зарегистрированных пользователей.

Раздел: Обзоры

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

УДК: 616.13/14:611.018.74

Библиографическая ссылка: Клиническая физиология кровообращения. 2025; 22 (1): 33-46

Цитировать как: Цыган В.Н., Санников А.Б. . Молекулярные сенсоры трансдукции напряжения сдвига эндотелиальных клеток сосудистой стенки. Клиническая физиология кровообращения. 2025; 22 (1): 33-46. DOI: 10.24022/1814-6910-2025-22-1-33-46

Ключевые слова: эндотелиальная клетка, механотрансдукция, механосенсоры, внеклеточный матрикс, гликокаликс, αVβ3-интегрины, коннексоны, ионные каналы PIEZO, внутриклеточная передача сигналов

Поступила / Принята к печати:  02.02.2025 / 19.02.2025

Скачать (Download)


Аннотация

Дальнейшее изучение различных аспектов биологии эндотелиальных клеток (ECs) остается актуальной задачей научных исследований, так как не только проясняет процессы реологического гемостаза в физиологических условиях, но и является ключом к пониманию механизмов развития практически всех сердечно-сосудистых заболеваний. Одним из основных факторов, способных оказать существенное влияние на функциональное состояние эндотелия сосудистой стенки в гемодинамических условиях, является изменение напряжения сдвига (Shear Stress – SS). Процесс изменения биохимической активности ECs под воздействием данного механического, с точки зрения биофизики, фактора получил название механотрансдукции. Для восприятия механических сигналов, инициирующих дальнейший внутриклеточный каскад событий вплоть до транскрипционных изменений, ЕСs должны иметь на своей поверхности механизмы, обладающие сенсорными способностями. Согласно современным данным, в качестве первичных механосенсоров рассматривается большое количество белковых молекул, локализованных в экстрацеллюлярном матриксе (ECM), гликокаликсе (GCX) и плазматической мембране (PM). Среди основных таких белков можно выделить: фибронектин; гликозаминогликаны синдекан и глипикан; гиалодерин CD44 и гиалуронан; входящие в состав адгезонов αVβ3-интегрины; коннексоны; механочувствительные ионные каналы PIEZO1 и большое количество протеинкиназ, каскадная активация которых при поступлении сигнала снаружи клетки внутрь составляет основу двух основных сигнальных путей дальнейшей внутриклеточной трансмиссии: Ras/ Raf/MEK/ERK и PI3K/AKT/mTOR.

В обзоре представлен материал, обобщающий современные данные о молекулярном строении и степени вовлеченности различных белковых молекул эндотелиальных клеток в качестве первичных сенсоров механического сигнала и его дальнейшей внутриклеточной трансдукции.

Литература

  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

Об авторах

  • Цыган Василий Николаевич, академик РАЕН, д-р мед. наук, профессор, заведующий кафедрой патологической физиологии имени В.В.Пашутина; ORCID
  • Санников Александр Борисович, канд. мед. наук, врач-ангиолог, сосудистый хирург; ORCID

 Если вы заметили опечатку, выделите текст и нажмите Alt+A