Endothelial shear stress responses: mechanotransduction, cell stress and adaptation
Keywords:
endothelium, shear stress, mechanotransduction, cell stress, adaptation.
Abstract
Endothelial cells lining the walls of blood vessels are one of the most important regulatory elements of the circulatory system. These mechanosensitive cells are in a direct contact with the flow of blood and able to detect deformation through its tangential component (shear) and the component directed along the normal to the surface (tension). Shear stress is the key inducer of the complex of signaling pathways mediated by tyrosine kinases, integrins, ion channels, involving also membrane lipids, glycocalyx and other cellular components. There are large amount of data on signal transduction in the literature, but less attention is paid to cellular adaptation to shear stress and there is relatively little information on the involvement of stress response genes in that process. Hydrodynamic conditions in certain zones of the vascular system are characterized by considerable heterogeneity, which can lead to weakening of feedbacks necessary for maintaining homeostasis in endothelial cells. This can contribute to the development of diseases such as atherosclerosis. This review presents new aspects and concepts related to the responses of endotheliocytes to shear stress and, in addition, highlights the basic methods of analyzing the effects of shear stress in vitro. Purpose of the study. Generalization of modern data on mechanisms of mechanosensitivity and mechanotransduction of the endothelium. Results. The review outlines the main mechanosensitivity mechanisms of endothelial cells, the pathways of intracellular signaling, the involvement of mechanisms of cellular stress response and adaptation. There are descriptions of experiments in which the molecular basis of mechanotransduction is identified, including the determination of proteins and other molecules involved in detection, signal transduction, and cellular response to shear stress.
Downloads
Download data is not yet available.
References
1. Chien S (2007) Mechanotransduction and endothelial cell homeostasis: the wisdom of the cell. American Journal of Physiology-Heart and Circulatory Physiology. 292: H1209-H1224.
2. Hahn C, Schwartz MA (2009) Mechanotransduction in vascular physiology and atherogenesis. Nature reviews Molecular cell biology. 10: 53-62.
3. Davies PF, Civelek M, Fang Y, Fleming I (2013) The atherosusceptible endothelium: endothelial phenotypes in complex haemodynamic shear stress regions in vivo. Cardiovascular research: cvt101.
4. Geiger B, Spatz JP, Bershadsky AD (2009) Environmental sensing through focal adhesions. Nature reviews Molecular cell biology. 10: 21.
5. Davies PF (1995) Flow-mediated endothelial mechanotransduction. Physiological reviews, 75: 519-60.
6. Weinbaum S, Tarbell JM, Damiano ER (2007) The structure and function of the endothelial glycocalyx layer. Annu Rev Biomed Eng, 9: 121-67.
7. Vink H, Duling BR (1996) Identification of Distinct Luminal Domains for Macromolecules, Erythrocytes, and Leukocytes Within Mammalian Capillaries. Circulation Research. 79: 581-9. Available: http://circres.ahajournals.org/content/79/3/581.
8. Feng J, Weinbaum S (2000) Lubrication theory in highly compressible porous media: the mechanics of skiing, from red cells to humans. Journal of Fluid Mechanics. 422: 281-317.
9. Bernfield M, Gotte M, Park PW, Reizes O, Fitzgerald ML, et al. (1999) Functions of cell surface heparan sulfate proteoglycans. Annual review of biochemistry. 68: 729-77.
10. Liebersbach BF, Sanderson RD (1994) Expression of syndecan-1 inhibits cell invasion into type I collagen. Journal of Biological Chemistry. 269: 20013-9.
11. Squire JM, Chew M, Nneji G, Neal C, Barry J, et al. (2001) Quasi-periodic substructure in the microvessel endothelial glycocalyx: a possible explanation for molecular filtering? Journal of structural biology. 136: 239-55.
12. Thi MM, Tarbell JM, Weinbaum S, Spray DC (2004) The role of the glycocalyx in reorganization of the actin cytoskeleton under fluid shear stress: a «bumper-car» model. Proceedings of the National Academy of Sciences of the United States of America. 101: 16483-8.
13. Zeng Y, Tarbell JM (2014) The adaptive remodeling of endothelial glycocalyx in response to fluid shear stress. PloS one. 9: e86249.
14. Tzima E, Del Pozo MA, Shattil SJ, Chien S, Schwartz MA (2001) Activation of integrins in endothelial cells by fluid shear stress mediates Rho-dependent cytoskeletal alignment. The EMBO journal. 20: 4639-47.
15. Ren X-D, Kiosses WB, Schwartz MA (1999) Regulation of the small GTP-binding protein Rho by cell adhesion and the cytoskeleton. The EMBO journal. 18: 578-85.
16. Davies PF, Robotewskyj A, Griem ML (1994) Quantitative studies of endothelial cell adhesion. Directional remodeling of focal adhesion sites in response to flow forces. Journal of Clinical Investigation. 93: 2031.
17. Katsumi A, Orr AW, Tzima E, Schwartz MA (2004) Integrins in mechanotransduction. Journal of Biological Chemistry. 279: 12001-4.
18. Kanchanawong P, Shtengel G, Pasapera AM, Ramko EB, Davidson MW, et al. (2010) Nanoscale architecture of integrin-based cell adhesions. Nature. 468: 580-84.
19. Li Y-SJ, Haga JH, Chien S (2005) Molecular basis of the effects of shear stress on vascular endothelial cells. Journal of biomechanics. 38: 1949-71.
20. Wang Y, Miao H, Li S, Chen K-D, Li Y-S, et al. (2002) Interplay between integrins and FLK-1 in shear stress-induced signaling. American Journal of Physiology-Cell Physiology. 283: C1540-C7.
21. Del Rio A, Perez-Jimenez R, Liu R, Roca-Cusachs P, Fernandez JM, et al. (2009) Stretching single talin rod molecules activates vinculin binding. Science. 323: 638-41.
22. Liu Z, Tan JL, Cohen DM, Yang MT, Sniadecki NJ, et al. (2010) Mechanical tugging force regulates the size of cell-cell junctions. Proceedings of the National Academy of Sciences. 107: 9944-9.
23. Gulino-Debrac D (2013) Mechanotransduction at the basis of endothelial barrier function. Tissue barriers. 1: e24180.
24. Woodfin A, Voisin M-B, Nourshargh S (2007) PECAM-1: a multi-functional molecule in inflammation and vascular biology. Arteriosclerosis, thrombosis, and vascular biology. 27: 2514-2523.
25. Tzima E, Irani-Tehrani M, Kiosses WB, Dejana E, Schultz DA, et al. (2005) A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature.437: 426-431.
26. Fleming I, Fisslthaler B, Dixit M, Busse R (2005) Role of PECAM-1 in the shear-stress-induced activation of Akt and the endothelial nitric oxide synthase (eNOS) in endothelial cells. Journal of cell science. 118: 4103-11.
27. Conway DE, Breckenridge MT, Hinde E, Gratton E, Chen CS, et al. (2013) Fluid shear stress on endothelial cells modulates mechanical tension across VE-cadherin and PECAM-1. Current Biology. 23: 1024-30.
28. Hur SS, Del Alamo JC, Park JS, Li Y-S, Nguyen HA, et al. (2012) Roles of cell confluency and fluid shear in 3-dimensional intracellular forces in endothelial cells. Proceedings of the National Academy of Sciences. 109: 11110-5.
29. Gerhold KA, Schwartz MA (2016) Ion Channels in Endothelial Responses to Fluid Shear Stress. Physiology. 31: 359-69.
30. Griffith TM (2004) Endothelium-dependent smooth muscle hyperpolarization: do gap junctions provide a unifying hypothesis? British journal of pharmacology. 141: 881-903.
31. Hoger JH, Ilyin VI, Forsyth S, Hoger A (2002) Shear stress regulates the endothelial Kir2. 1 ion channel. Proceedings of the National Academy of Sciences. 99: 7780-5.
32. Wu J, Lewis AH, Grandl J (2017) Touch, Tension, and Transduction-The Function and Regulation of Piezo Ion Channels. Trends in biochemical sciences. 42: 57-71.
33. Garc`ia-Cardena G, Comander J, Anderson KR, Blackman BR, Gimbrone MA (2001) Biomechanical activation of vascular endothelium as a determinant of its functional phenotype. Proceedings of the National Academy of Sciences. 98: 4478-85.
34. Liu C, Bhattacharjee G, Boisvert W, Dilley R, Edgington T (2003) In vivo interrogation of the molecular display of atherosclerotic lesion surfaces. The American journal of pathology. 163: 1859-71.
35. Zhou J, Werstuck GH, Lhotak/vSarka, de Koning AL, Sood SK, et al. (2004) Association of multiple cellular stress pathways with accelerated atherosclerosis in hyperhomocysteinemic apolipoprotein E-deficient mice. Circulation. 110: 207-13.
36. Bhattacharjee G, Ahamed J, Pedersen B, El-Sheikh A, Mackman N, et al. (2005) Regulation of tissue factor-mediated initiation of the coagulation cascade by cell surface grp78. Arteriosclerosis, thrombosis, and vascular biology. 25: 1737-43.
37. Zhou J, Lhotak/vSarka, Hilditch BA, Austin RC (2005) Activation of the unfolded protein response occurs at all stages of atherosclerotic lesion development in apolipoprotein E-deficient mice. Circulation. 111: 1814-21.
38. Feaver RE, Hastings NE, Pryor A, Blackman BR (2008) GRP78 upregulation by atheroprone shear stress via p38-, $\alpha$2$\beta$1-dependent mechanism in endothelial cells. Arteriosclerosis, thrombosis, and vascular biology. 28: 1534-41.
39. Rigg RA, Healy LD, Nowak MS, Mallet J, Thierheimer ML, et al. (2016) Heat shock protein 70 regulates platelet integrin activation, granule secretion and aggregation. American Journal of Physiology-Cell Physiology. 310: C568-C75.
40. Mitrea DM, Kriwacki RW (2013) Regulated unfolding of proteins in signaling. FEBS letters. 587: 1081-8.
41. Vogel V (2006) Mechanotransduction involving multimodular proteins: converting force into biochemical signals. Annu Rev Biophys Biomol Struct. 35: 459-88.
42. Bao G, Kamm RD, Thomas W, Hwang W, Fletcher DA, et al. (2010) Molecular biomechanics: the molecular basis of how forces regulate cellular function. Cellular and Molecular Bioengineering. 3: 91-105.
43. Ignashkova T, Mesitov M, Rybakov A, Moskovtsev A, Sokolovskaia A, et al. Deposition of von Willebrand factor in human endothelial cells HUVEC in the endoplasmic reticulum stress induced by an excess of homocysteine in vitro. Patologicheskaia fiziologiya i eksperimental’naya terapiya. 2012; 3: 81-6. (in Russian)
44. Chiu J-J, Chien S (2011) Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives. Physiological reviews. 91: 327-87.
45. Kolesov D, Moskovtsev A, Mylnikova AN, Savina G, Sokolovskaya A, et al. (2016) Biomodeling of microvessels in a microfluidic chip. Pathogenesis. 14: 4-8.
46. Chau L, Doran M, Cooper-White J (2009) A novel multishear microdevice for studying cell mechanics. Lab on a Chip. 9: 1897-902.
47. Tsou JK, Gower RM, Ting HJ, Schaff UY, Insana MF, et al. (2008) Spatial regulation of inflammation by human aortic endothelial cells in a linear gradient of shear stress. Microcirculation. 15: 311-23.
48. Folkman J, Haudenschild CC, Zetter BR (1979) Long-term culture of capillary endothelial cells. Proceedings of the National Academy of Sciences. 76: 5217-21.
49. Weinberg CB, Bell E (1986) A blood vessel model constructed from collagen and cultured vascular cells. Science. 231: 397-400.
50. Chrobak KM, Potter DR, Tien J (2006) Formation of perfused, functional microvascular tubes in vitro. Microvascular research. 71: 185-96.
2. Hahn C, Schwartz MA (2009) Mechanotransduction in vascular physiology and atherogenesis. Nature reviews Molecular cell biology. 10: 53-62.
3. Davies PF, Civelek M, Fang Y, Fleming I (2013) The atherosusceptible endothelium: endothelial phenotypes in complex haemodynamic shear stress regions in vivo. Cardiovascular research: cvt101.
4. Geiger B, Spatz JP, Bershadsky AD (2009) Environmental sensing through focal adhesions. Nature reviews Molecular cell biology. 10: 21.
5. Davies PF (1995) Flow-mediated endothelial mechanotransduction. Physiological reviews, 75: 519-60.
6. Weinbaum S, Tarbell JM, Damiano ER (2007) The structure and function of the endothelial glycocalyx layer. Annu Rev Biomed Eng, 9: 121-67.
7. Vink H, Duling BR (1996) Identification of Distinct Luminal Domains for Macromolecules, Erythrocytes, and Leukocytes Within Mammalian Capillaries. Circulation Research. 79: 581-9. Available: http://circres.ahajournals.org/content/79/3/581.
8. Feng J, Weinbaum S (2000) Lubrication theory in highly compressible porous media: the mechanics of skiing, from red cells to humans. Journal of Fluid Mechanics. 422: 281-317.
9. Bernfield M, Gotte M, Park PW, Reizes O, Fitzgerald ML, et al. (1999) Functions of cell surface heparan sulfate proteoglycans. Annual review of biochemistry. 68: 729-77.
10. Liebersbach BF, Sanderson RD (1994) Expression of syndecan-1 inhibits cell invasion into type I collagen. Journal of Biological Chemistry. 269: 20013-9.
11. Squire JM, Chew M, Nneji G, Neal C, Barry J, et al. (2001) Quasi-periodic substructure in the microvessel endothelial glycocalyx: a possible explanation for molecular filtering? Journal of structural biology. 136: 239-55.
12. Thi MM, Tarbell JM, Weinbaum S, Spray DC (2004) The role of the glycocalyx in reorganization of the actin cytoskeleton under fluid shear stress: a «bumper-car» model. Proceedings of the National Academy of Sciences of the United States of America. 101: 16483-8.
13. Zeng Y, Tarbell JM (2014) The adaptive remodeling of endothelial glycocalyx in response to fluid shear stress. PloS one. 9: e86249.
14. Tzima E, Del Pozo MA, Shattil SJ, Chien S, Schwartz MA (2001) Activation of integrins in endothelial cells by fluid shear stress mediates Rho-dependent cytoskeletal alignment. The EMBO journal. 20: 4639-47.
15. Ren X-D, Kiosses WB, Schwartz MA (1999) Regulation of the small GTP-binding protein Rho by cell adhesion and the cytoskeleton. The EMBO journal. 18: 578-85.
16. Davies PF, Robotewskyj A, Griem ML (1994) Quantitative studies of endothelial cell adhesion. Directional remodeling of focal adhesion sites in response to flow forces. Journal of Clinical Investigation. 93: 2031.
17. Katsumi A, Orr AW, Tzima E, Schwartz MA (2004) Integrins in mechanotransduction. Journal of Biological Chemistry. 279: 12001-4.
18. Kanchanawong P, Shtengel G, Pasapera AM, Ramko EB, Davidson MW, et al. (2010) Nanoscale architecture of integrin-based cell adhesions. Nature. 468: 580-84.
19. Li Y-SJ, Haga JH, Chien S (2005) Molecular basis of the effects of shear stress on vascular endothelial cells. Journal of biomechanics. 38: 1949-71.
20. Wang Y, Miao H, Li S, Chen K-D, Li Y-S, et al. (2002) Interplay between integrins and FLK-1 in shear stress-induced signaling. American Journal of Physiology-Cell Physiology. 283: C1540-C7.
21. Del Rio A, Perez-Jimenez R, Liu R, Roca-Cusachs P, Fernandez JM, et al. (2009) Stretching single talin rod molecules activates vinculin binding. Science. 323: 638-41.
22. Liu Z, Tan JL, Cohen DM, Yang MT, Sniadecki NJ, et al. (2010) Mechanical tugging force regulates the size of cell-cell junctions. Proceedings of the National Academy of Sciences. 107: 9944-9.
23. Gulino-Debrac D (2013) Mechanotransduction at the basis of endothelial barrier function. Tissue barriers. 1: e24180.
24. Woodfin A, Voisin M-B, Nourshargh S (2007) PECAM-1: a multi-functional molecule in inflammation and vascular biology. Arteriosclerosis, thrombosis, and vascular biology. 27: 2514-2523.
25. Tzima E, Irani-Tehrani M, Kiosses WB, Dejana E, Schultz DA, et al. (2005) A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature.437: 426-431.
26. Fleming I, Fisslthaler B, Dixit M, Busse R (2005) Role of PECAM-1 in the shear-stress-induced activation of Akt and the endothelial nitric oxide synthase (eNOS) in endothelial cells. Journal of cell science. 118: 4103-11.
27. Conway DE, Breckenridge MT, Hinde E, Gratton E, Chen CS, et al. (2013) Fluid shear stress on endothelial cells modulates mechanical tension across VE-cadherin and PECAM-1. Current Biology. 23: 1024-30.
28. Hur SS, Del Alamo JC, Park JS, Li Y-S, Nguyen HA, et al. (2012) Roles of cell confluency and fluid shear in 3-dimensional intracellular forces in endothelial cells. Proceedings of the National Academy of Sciences. 109: 11110-5.
29. Gerhold KA, Schwartz MA (2016) Ion Channels in Endothelial Responses to Fluid Shear Stress. Physiology. 31: 359-69.
30. Griffith TM (2004) Endothelium-dependent smooth muscle hyperpolarization: do gap junctions provide a unifying hypothesis? British journal of pharmacology. 141: 881-903.
31. Hoger JH, Ilyin VI, Forsyth S, Hoger A (2002) Shear stress regulates the endothelial Kir2. 1 ion channel. Proceedings of the National Academy of Sciences. 99: 7780-5.
32. Wu J, Lewis AH, Grandl J (2017) Touch, Tension, and Transduction-The Function and Regulation of Piezo Ion Channels. Trends in biochemical sciences. 42: 57-71.
33. Garc`ia-Cardena G, Comander J, Anderson KR, Blackman BR, Gimbrone MA (2001) Biomechanical activation of vascular endothelium as a determinant of its functional phenotype. Proceedings of the National Academy of Sciences. 98: 4478-85.
34. Liu C, Bhattacharjee G, Boisvert W, Dilley R, Edgington T (2003) In vivo interrogation of the molecular display of atherosclerotic lesion surfaces. The American journal of pathology. 163: 1859-71.
35. Zhou J, Werstuck GH, Lhotak/vSarka, de Koning AL, Sood SK, et al. (2004) Association of multiple cellular stress pathways with accelerated atherosclerosis in hyperhomocysteinemic apolipoprotein E-deficient mice. Circulation. 110: 207-13.
36. Bhattacharjee G, Ahamed J, Pedersen B, El-Sheikh A, Mackman N, et al. (2005) Regulation of tissue factor-mediated initiation of the coagulation cascade by cell surface grp78. Arteriosclerosis, thrombosis, and vascular biology. 25: 1737-43.
37. Zhou J, Lhotak/vSarka, Hilditch BA, Austin RC (2005) Activation of the unfolded protein response occurs at all stages of atherosclerotic lesion development in apolipoprotein E-deficient mice. Circulation. 111: 1814-21.
38. Feaver RE, Hastings NE, Pryor A, Blackman BR (2008) GRP78 upregulation by atheroprone shear stress via p38-, $\alpha$2$\beta$1-dependent mechanism in endothelial cells. Arteriosclerosis, thrombosis, and vascular biology. 28: 1534-41.
39. Rigg RA, Healy LD, Nowak MS, Mallet J, Thierheimer ML, et al. (2016) Heat shock protein 70 regulates platelet integrin activation, granule secretion and aggregation. American Journal of Physiology-Cell Physiology. 310: C568-C75.
40. Mitrea DM, Kriwacki RW (2013) Regulated unfolding of proteins in signaling. FEBS letters. 587: 1081-8.
41. Vogel V (2006) Mechanotransduction involving multimodular proteins: converting force into biochemical signals. Annu Rev Biophys Biomol Struct. 35: 459-88.
42. Bao G, Kamm RD, Thomas W, Hwang W, Fletcher DA, et al. (2010) Molecular biomechanics: the molecular basis of how forces regulate cellular function. Cellular and Molecular Bioengineering. 3: 91-105.
43. Ignashkova T, Mesitov M, Rybakov A, Moskovtsev A, Sokolovskaia A, et al. Deposition of von Willebrand factor in human endothelial cells HUVEC in the endoplasmic reticulum stress induced by an excess of homocysteine in vitro. Patologicheskaia fiziologiya i eksperimental’naya terapiya. 2012; 3: 81-6. (in Russian)
44. Chiu J-J, Chien S (2011) Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives. Physiological reviews. 91: 327-87.
45. Kolesov D, Moskovtsev A, Mylnikova AN, Savina G, Sokolovskaya A, et al. (2016) Biomodeling of microvessels in a microfluidic chip. Pathogenesis. 14: 4-8.
46. Chau L, Doran M, Cooper-White J (2009) A novel multishear microdevice for studying cell mechanics. Lab on a Chip. 9: 1897-902.
47. Tsou JK, Gower RM, Ting HJ, Schaff UY, Insana MF, et al. (2008) Spatial regulation of inflammation by human aortic endothelial cells in a linear gradient of shear stress. Microcirculation. 15: 311-23.
48. Folkman J, Haudenschild CC, Zetter BR (1979) Long-term culture of capillary endothelial cells. Proceedings of the National Academy of Sciences. 76: 5217-21.
49. Weinberg CB, Bell E (1986) A blood vessel model constructed from collagen and cultured vascular cells. Science. 231: 397-400.
50. Chrobak KM, Potter DR, Tien J (2006) Formation of perfused, functional microvascular tubes in vitro. Microvascular research. 71: 185-96.
Published
2017-12-18
How to Cite
Moskovtsev A. A., Kolesov D. V., Mylnikova A. N., Zaychenko D. M., Sokolovskaya A. A., Kubatiev A. A. Endothelial shear stress responses: mechanotransduction, cell stress and adaptation // Patologicheskaya Fiziologiya i Eksperimental’naya Terapiya (Pathological physiology and experimental therapy). 2017. VOL. 61. № 4. PP. 112–125.
Issue
Section
Reviews
