Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Shear Stress and Atherosclerosis

  • Heo, Kyung-Sun (Aab Cardiovascular Research Institute, University of Rochester) ;
  • Fujiwara, Keigi (Aab Cardiovascular Research Institute, University of Rochester) ;
  • Abe, Jun-Ichi (Aab Cardiovascular Research Institute, University of Rochester)
  • Received : 2014.04.03
  • Accepted : 2014.04.07
  • Published : 2014.06.30
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Abstract

Hemodynamic shear stress, the frictional force acting on vascular endothelial cells, is crucial for endothelial homeostasis under normal physiological conditions. When discussing blood flow effects on various forms of endothelial (dys)function, one considers two flow patterns: steady laminar flow and disturbed flow because endothelial cells respond differently to these flow types both in vivo and in vitro. Laminar flow which exerts steady laminar shear stress is atheroprotective while disturbed flow creates an atheroprone environment. Emerging evidence has provided new insights into the cellular mechanisms of flowdependent regulation of vascular function that leads to cardiovascular events such as atherosclerosis, atherothrombosis, and myocardial infarction. In order to study effects of shear stress and different types of flow, various models have been used. In this review, we will summarize our current views on how disturbed flow-mediated signaling pathways are involved in the development of atherosclerosis.

Keywords

References

  1. Akaike, M., Che, W., Marmarosh, N.L., Ohta, S., Osawa, M., Ding, B., Berk, B.C., Yan, C., and Abe, J. (2004). The hinge-helix 1 region of peroxisome proliferator-activated receptor gamma1 (PPARgamma1) mediates interaction with extracellular signalregulated kinase 5 and PPARgamma1 transcriptional activation: involvement in flow-induced PPARgamma activation in endothelial cells. Mol. Cell. Biol. 24, 8691-8704. https://doi.org/10.1128/MCB.24.19.8691-8704.2004
  2. Ando, J., and Yamamoto, K. (2009). Vascular mechanobiology: endothelial cell responses to fluid shear stress. Circ. J. 73, 1983-1992. https://doi.org/10.1253/circj.CJ-09-0583
  3. Barakat, A.I. (1999). Responsiveness of vascular endothelium to shear stress: potential role of ion channels and cellular cytoskeleton (review). Int. J. Mol. Med. 4, 323-332.
  4. Barton, M., Baretella, O., and Meyer, M.R. (2012). Obesity and risk of vascular disease: importance of endothelium-dependent vasoconstriction. Br. J. Pharmacol. 165, 591-602. https://doi.org/10.1111/j.1476-5381.2011.01472.x
  5. Berk, B.C., Min, W., Yan, C., Surapisitchat, J., Liu, Y., and Hoefen, R. (2002). Atheroprotective mechanisms activated by fluid shear stress in endothelial cells. Drug News Perspect. 15, 133-139. https://doi.org/10.1358/dnp.2002.15.3.704684
  6. Boo, Y.C., Hwang, J., Sykes, M., Michell, B.J., Kemp, B.E., Lum, H., and Jo, H. (2002). Shear stress stimulates phosphorylation of eNOS at Ser(635) by a protein kinase A-dependent mechanism. Am. J. Physiol. Heart Circ. Physiol. 283, H1819-1828. https://doi.org/10.1152/ajpheart.00214.2002
  7. Chang, E., Heo, K.S., Woo, C.H., Lee, H., Le, N.T., Thomas, T.N., Fujiwara, K., and Abe, J. (2011). MK2 SUMOylation regulates actin filament remodeling and subsequent migration in endothelial cells by inhibiting MK2 kinase and HSP27 phosphorylation. Blood 117, 2527-2537. https://doi.org/10.1182/blood-2010-08-302281
  8. Cheng, J., Wang, D., Wang, Z., and Yeh, E.T. (2004). SENP1 enhances androgen receptor-dependent transcription through desumoylation of histone deacetylase 1. Mol. Cell. Biol. 24, 6021-6028. https://doi.org/10.1128/MCB.24.13.6021-6028.2004
  9. Chiu, Y.J., Kusano, K., Thomas, T.N., and Fujiwara, K. (2004). Endothelial cell-cell adhesion and mechanosignal transduction. Endothelium 11, 59-73. https://doi.org/10.1080/10623320490432489
  10. Chiu, S.Y., Asai, N., Costantini, F., and Hsu, W. (2008a). SUMO-specific protease 2 is essential for modulating p53-Mdm2 in development of trophoblast stem cell niches and lineages. PLoS Biol. 6, e310. https://doi.org/10.1371/journal.pbio.0060310
  11. Chiu, Y.J., McBeath, E., and Fujiwara, K. (2008b). Mechanotransduction in an extracted cell model: Fyn drives stretch- and flow-elicited PECAM-1 phosphorylation. J. Cell Biol. 182, 753-763. https://doi.org/10.1083/jcb.200801062
  12. Conway, D., and Schwartz, M.A. (2012). Lessons from the endothelial junctional mechanosensory complex. F1000 Biol. Rep. 4, 1.
  13. Curry, F.E., and Adamson, R.H. (2012). Endothelial glycocalyx: permeability barrier and mechanosensor. Ann. Biomed. Eng. 40, 828-839. https://doi.org/10.1007/s10439-011-0429-8
  14. Davies, P.F. (2009). Hemodynamic shear stress and the endothelium in cardiovascular pathophysiology. Nat. Clin. Pract. Cardiovasc. Med. 6, 16-26. https://doi.org/10.1038/ncpcardio1397
  15. Davies, M.J., Gordon, J.L., Gearing, A.J., Pigott, R., Woolf, N., Katz, D., and Kyriakopoulos, A. (1993). The expression of the adhesion molecules ICAM-1, VCAM-1, PECAM, and E- selectin in human atherosclerosis. J. Pathol. 171, 223-229. https://doi.org/10.1002/path.1711710311
  16. Davis, M.E., Cai, H., Drummond, G.R., and Harrison, D.G. (2000). Regulation of endothelial nitric oxide synthase (eNOS) expression by laminar shear stress (abstract). Circulation 102, II-117.
  17. Davis, M.E., Cai, H., Drummond, G.R., and Harrison, D.G. (2001). Shear stress regulates endothelial nitric oxide synthase expression through c-Src by divergent signaling pathways. Circ. Res. 89, 1073-1080. https://doi.org/10.1161/hh2301.100806
  18. Dixit, M., Loot, A.E., Mohamed, A., Fisslthaler, B., Boulanger, C.M., Ceacareanu, B., Hassid, A., Busse, R., and Fleming, I. (2005). Gab1, SHP2, and protein kinase A are crucial for the activation of the endothelial NO synthase by fluid shear stress. Circ. Res. 97, 1236-1244. https://doi.org/10.1161/01.RES.0000195611.59811.ab
  19. Fleming, I., Fisslthaler, B., Dixit, M., and 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. J. Cell Sci. 118, 4103-4111. https://doi.org/10.1242/jcs.02541
  20. Garin, G., Abe, J.I., Mohan, A., Lu, W., Yan, C., Newby, A.C., Rhaman, A., and Berk, B.C. (2007). Flow antagonizes TNF-alpha signaling in endothelial cells by inhibiting caspase-dependent PKC zeta processing. Circ. Res. 101, 97-105. https://doi.org/10.1161/CIRCRESAHA.107.148270
  21. Geiss-Friedlander, R., and Melchior, F. (2007). Concepts in sumoylation: a decade on. Nat. Rev. Mol. Cell. Biol. 8, 947-956. https://doi.org/10.1038/nrm2293
  22. Goel, R., Schrank, B.R., Arora, S., Boylan, B., Fleming, B., Miura, H., Newman, P.J., Molthen, R.C., and Newman, D.K. (2008). Site-specific effects of PECAM-1 on atherosclerosis in LDL receptor-deficient mice. Arterioscler. Thromb. Vasc. Biol. 28, 1996-2002. https://doi.org/10.1161/ATVBAHA.108.172270
  23. Gudi, S., Huvar, I., White, C.R., McKnight, N.L., Dusserre, N., Boss, G.R., and Frangos, J.A. (2003). Rapid activation of Ras by fluid flow is mediated by Galpha(q) and Gbetagamma subunits of heterotrimeric G proteins in human endothelial cells. Arterioscler. Thromb. Vasc. Biol. 23, 994-1000. https://doi.org/10.1161/01.ATV.0000073314.51987.84
  24. Hajra, L., Evans, A.I., Chen, M., Hyduk, S.J., Collins, T., and Cybulsky, M.I. (2000). The NF-kappa B signal transduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerotic lesion formation. Proc. Natl. Acad. Sci. USA 97, 9052-9057. https://doi.org/10.1073/pnas.97.16.9052
  25. Harry, B.L., Sanders, J.M., Feaver, R.E., Lansey, M., Deem, T.L., Zarbock, A., Bruce, A.C., Pryor, A.W., Gelfand, B.D., Blackman, B.R., et al. (2008). Endothelial cell PECAM-1 promotes atherosclerotic lesions in areas of disturbed flow in ApoE-deficient mice. Arterioscler. Thromb. Vasc. Biol. 28, 2003-2008. https://doi.org/10.1161/ATVBAHA.108.164707
  26. Helmke, B.P., Goldman, R.D., and Davies, P.F. (2000). Rapid displacement of vimentin intermediate filaments in living endothelial cells exposed to flow. Circ. Res. 86, 745-752. https://doi.org/10.1161/01.RES.86.7.745
  27. Heo, K.S., Fujiwara, K., and Abe, J. (2011a). Disturbed-flow-mediated vascular reactive oxygen species induce endothelial dysfunction. Circ. J. 75, 2722-2730. https://doi.org/10.1253/circj.CJ-11-1124
  28. Heo, K.S., Lee, H., Nigro, P., Thomas, T., Le, N.T., Chang, E., McClain, C., Reinhart-King, C.A., King, M.R., Berk, B.C., et al. (2011b). PKCzeta mediates disturbed flow-induced endothelial apoptosis via p53 SUMOylation. J. Cell Biol. 193, 867-884. https://doi.org/10.1083/jcb.201010051
  29. Heo, K.S., Chang, E., Le, N.T., Cushman, H.J., Yeh, E.T.H., Fujiwara, K., and Abe, J.I. (2013). De-SUMOylation enzyme of sentrin/SUMO-specific protease 2 regulates disturbed flow-induced SUMOylation of ERK5 and p53 that leads to endothelial dysfunction and atherosclerosis. Circ. Res. 112, 911-923. https://doi.org/10.1161/CIRCRESAHA.111.300179
  30. Iiyama, K., Hajra, L., Iiyama, M., Li, H., DiChiara, M., Medoff, B.D., and Cybulsky, M.I. (1999). Patterns of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in rabbit and mouse atherosclerotic lesions and at sites predisposed to lesion formation. Circ. Res. 85, 199-207. https://doi.org/10.1161/01.RES.85.2.199
  31. Jalali, S., del Pozo, M.A., Chen, K., Miao, H., Li, Y., Schwartz, M.A., Shyy, J.Y., and Chien, S. (2001). Integrin-mediated mechanotransduction requires its dynamic interaction with specific extracellular matrix (ECM) ligands. Proc. Natl. Acad. Sci. USA 98, 1042-1046. https://doi.org/10.1073/pnas.98.3.1042
  32. Jiang, M., Chiu, S.Y., and Hsu, W. (2011). SUMO-specific protease 2 in Mdm2-mediated regulation of p53. Cell Death Differ. 18, 1005-1015. https://doi.org/10.1038/cdd.2010.168
  33. Johnson, B.D., Mather, K.J., and Wallace, J.P. (2011). Mechanotransduction of shear in the endothelium: basic studies and clinical implications. Vasc. Med. 16, 365-377. https://doi.org/10.1177/1358863X11422109
  34. Jongstra-Bilen, J., Haidari, M., Zhu, S.N., Chen, M., Guha, D., and Cybulsky, M.I. (2006). Low-grade chronic inflammation in regions of the normal mouse arterial intima predisposed to atherosclerosis. J. Exp. Med. 203, 2073-2083. https://doi.org/10.1084/jem.20060245
  35. Kano, Y., Katoh, K., and Fujiwara, K. (2000). Lateral zone of cell-cell adhesion as the major fluid shear stress-related signal transduction site. Circ. Res. 86, 425-433. https://doi.org/10.1161/01.RES.86.4.425
  36. Koskinas, K.C., Chatzizisis, Y.S., Antoniadis, A.P., and Giannoglou, G.D. (2012). Role of endothelial shear stress in stent restenosis and thrombosis: pathophysiologic mechanisms and implications for clinical translation. J. Am. Coll. Cardiol. 59, 1337-1349. https://doi.org/10.1016/j.jacc.2011.10.903
  37. Le, N.T., Heo, K.S., Takei, Y., Lee, H., Woo, C.H., Chang, E., McClain, C., Hurley, C., Wang, X., Li, F., et al. (2013). A crucial role for p90RSK-mediated reduction of ERK5 transcriptional activity in endothelial dysfunction and atherosclerosis. Circulation 127, 486-499. https://doi.org/10.1161/CIRCULATIONAHA.112.116988
  38. Liu, Y., Chen, B.P., Lu, M., Zhu, Y., Stemerman, M.B., Chien, S., and Shyy, J.Y. (2002). Shear stress activation of SREBP1 in endothelial cells is mediated by integrins. Arterioscler. Thromb. Vasc. Biol. 22, 76-81. https://doi.org/10.1161/hq0102.101822
  39. Michiels, C. (2003). Endothelial cell functions. J. Cell. Physiol. 196, 430-443. https://doi.org/10.1002/jcp.10333
  40. Nam, D., Ni, C.W., Rezvan, A., Suo, J., Budzyn, K., Llanos, A., Harrison, D., Giddens, D., and Jo, H. (2009). Partial carotid ligation is a model of acutely induced disturbed flow, leading to rapid endothelial dysfunction and atherosclerosis. Am. J. Physiol. Heart Circ. Physiol. 297, H1535-1543. https://doi.org/10.1152/ajpheart.00510.2009
  41. Nauli, S.M., Jin, X., AbouAlaiwi, W.A., El-Jouni, W., Su, X., and Zhou, J. (2013). Non-motile primary cilia as fluid shear stress mechanosensors. Methods Enzymol. 525, 1-20. https://doi.org/10.1016/B978-0-12-397944-5.00001-8
  42. Osawa, M., Masuda, M., Harada, N., Bruno Lopes, R., and Fujiwara, K. (1997). Tyrosine phosphorylation of platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) in mechanically stimulated vascular endothelial cells. Eur. J. Cell Biol. 72, 229-237.
  43. Osborn, E.A., Rabodzey, A., Dewey, C.F., Jr., and Hartwig, J.H. (2006). Endothelial actin cytoskeleton remodeling during mechanostimulation with fluid shear stress. Am. J. Physiol. Cell Physiol. 290, C444-452. https://doi.org/10.1152/ajpcell.00218.2005
  44. Pi, X., Yan, C., and Berk, B.C. (2004). Big mitogen-activated protein kinase (BMK1)/ERK5 protects endothelial cells from apoptosis. Circ. Res. 94, 362-369. https://doi.org/10.1161/01.RES.0000112406.27800.6F
  45. Reinhart-King, C.A., Fujiwara, K., and Berk, B.C. (2008). Physiologic stress-mediated signaling in the endothelium. Methods Enzymol. 443, 25-44. https://doi.org/10.1016/S0076-6879(08)02002-8
  46. Shyy, J.Y., and Chien, S. (2002). Role of integrins in endothelial mechanosensing of shear stress. Circ. Res. 91, 769-775. https://doi.org/10.1161/01.RES.0000038487.19924.18
  47. Stern, D.M., Esposito, C., Gerlach, H., Gerlach, M., Ryan, J., Handley, D., and Nawroth, P. (1991). Endothelium and regulation of coagulation. Diabetes Care 14, 160-166. https://doi.org/10.2337/diacare.14.2.160
  48. Traub, O., and Berk, B.C. (1998). Laminar shear stress: mechanisms by which endothelial cells transduce an atheroprotective force. Arterioscler. Thromb. Vasc. Biol. 18, 677-685. https://doi.org/10.1161/01.ATV.18.5.677
  49. Tzima, E., del Pozo, M.A., Shattil, S.J., Chien, S., and Schwartz, M.A. (2001). Activation of integrins in endothelial cells by fluid shear stress mediates Rho-dependent cytoskeletal alignment. EMBO J. 20, 4639-4647. https://doi.org/10.1093/emboj/20.17.4639
  50. Tzima, E., Irani-Tehrani, M., Kiosses, W.B., Dejana, E., Schultz, D.A., Engelhardt, B., Cao, G., DeLisser, H., and Schwartz, M.A. (2005). A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature 437, 426-431. https://doi.org/10.1038/nature03952
  51. Witty, J., Aguilar-Martinez, E., and Sharrocks, A.D. (2010). SENP1 participates in the dynamic regulation of Elk-1 SUMOylation. Biochem. J. 428, 247-254. https://doi.org/10.1042/BJ20091948
  52. Won, D., Zhu, S.N., Chen, M., Teichert, A.M., Fish, J.E., Matouk, C.C., Bonert, M., Ojha, M., Marsden, P.A., and Cybulsky, M.I. (2007). Relative reduction of endothelial nitric-oxide synthase expression and transcription in atherosclerosis-prone regions of the mouse aorta and in an in vitro model of disturbed flow. Am. J. Pathol. 171, 1691-1704. https://doi.org/10.2353/ajpath.2007.060860
  53. Woo, C.H., Massett, M.P., Shishido, T., Itoh, S., Ding, B., McClain, C., Che, W., Vulapalli, S.R., Yan, C., and Abe, J. (2006). ERK5 activation inhibits inflammatory responses via peroxisome proliferator-activated receptor delta (PPARdelta) stimulation. J. Biol. Chem. 281, 32164-32174. https://doi.org/10.1074/jbc.M602369200
  54. Woo, C.H., Shishido, T., McClain, C., Lim, J.H., Li, J.D., Yang, J., Yan, C., and Abe, J. (2008a). Extracellular signal-regulated kinase 5 SUMOylation antagonizes shear stress-induced anti-inflammatory response and endothelial nitric oxide synthase expression in endothelial cells. Circ. Res. 102, 538-545. https://doi.org/10.1161/CIRCRESAHA.107.156877
  55. Woo, C.H., Shishido, T., McClain, C., Lim, J.H., Li, J.D., Yang, J., Yan, C., and Abe, J. (2008b). Extracellular signal-regulated kinase 5 SUMOylation antagonizes shear stress-induced anti-inflammatory response and endothelial nitric oxide synthase expression in endothelial cells. Circ. Res. 102, 538-545. https://doi.org/10.1161/CIRCRESAHA.107.156877
  56. Yeh, E.T. (2009). SUMOylation and De-SUMOylation: wrestling with life's processes. J. Biol. Chem. 284, 8223-8227. https://doi.org/10.1074/jbc.R800050200
  57. Young, A., Wu, W., Sun, W., Benjamin Larman, H., Wang, N., Li, Y.S., Shyy, J.Y., Chien, S., and Garcia-Cardena, G. (2009). Flow activation of AMP-activated protein kinase in vascular endothelium leads to Kruppel-like factor 2 expression. Arterioscler. Thromb. Vasc. Biol. 29, 1902-1908. https://doi.org/10.1161/ATVBAHA.109.193540
  58. Yu, J., Bergaya, S., Murata, T., Alp, I.F., Bauer, M.P., Lin, M.I., Drab, M., Kurzchalia, T.V., Stan, R.V., and Sessa, W.C. (2006). Direct evidence for the role of caveolin-1 and caveolae in mechanotransduction and remodeling of blood vessels. J. Clin. Invest. 116, 1284-1291. https://doi.org/10.1172/JCI27100

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  44. Therapeutic targets and drugs for hyper-proliferation of vascular smooth muscle cells vol.50, pp.4, 2020, https://doi.org/10.1007/s40005-019-00469-5
  45. Endothelial monolayer disruption in bioprosthetic heart valve as a trigger of primary tissue failure vol.19, pp.2, 2014, https://doi.org/10.20538/1682-0363-2020-2-55-62
  46. Harnessing Mechanosensation in Next Generation Cardiovascular Tissue Engineering vol.10, pp.10, 2014, https://doi.org/10.3390/biom10101419
  47. Shear Stress in Schlemm’s Canal as a Sensor of Intraocular Pressure vol.10, pp.None, 2014, https://doi.org/10.1038/s41598-020-62730-4
  48. Endothelial Function in Patients With Continuous-Flow Left Ventricular Assist Devices vol.72, pp.1, 2021, https://doi.org/10.1177/0003319720946977
  49. Dendrobium catenatum Lindl. Water Extracts Attenuate Atherosclerosis vol.2021, pp.None, 2014, https://doi.org/10.1155/2021/9951946
  50. Reconstructing haemodynamics quantities of interest from Doppler ultrasound imaging vol.37, pp.2, 2014, https://doi.org/10.1002/cnm.3416
  51. Functional lipidomics of vascular endothelial cells in response to laminar shear stress vol.35, pp.2, 2021, https://doi.org/10.1096/fj.202002144r
  52. Endothelial Rap1 (Ras-Association Proximate 1) Restricts Inflammatory Signaling to Protect From the Progression of Atherosclerosis vol.41, pp.2, 2021, https://doi.org/10.1161/atvbaha.120.315401
  53. Dilation‐Responsive Microshape Programing Prevents Vascular Graft Stenosis vol.17, pp.18, 2014, https://doi.org/10.1002/smll.202007297
  54. Recent Developments in Nanomaterial‐Based Shear‐Sensitive Drug Delivery Systems vol.10, pp.13, 2014, https://doi.org/10.1002/adhm.202002196
  55. LXN deficiency regulates cytoskeleton remodelling by promoting proteolytic cleavage of Filamin A in vascular endothelial cells vol.25, pp.14, 2014, https://doi.org/10.1111/jcmm.16685
  56. Rosuvastatin Inhibits the Apoptosis of Platelet-Derived Growth Factor-Stimulated Vascular Smooth Muscle Cells by Inhibiting p38 via Autophagy vol.378, pp.1, 2014, https://doi.org/10.1124/jpet.121.000539
  57. The quiescent endothelium: signalling pathways regulating organ-specific endothelial normalcy vol.18, pp.8, 2014, https://doi.org/10.1038/s41569-021-00517-4
  58. Novel Biomarkers of Endothelial Dysfunction in Cardiovascular Diseases vol.17, pp.4, 2014, https://doi.org/10.20996/1819-6446-2021-08-08
  59. miR‐25‐5p regulates endothelial progenitor cell differentiation in response to shear stress through targeting ABCA1 vol.45, pp.9, 2014, https://doi.org/10.1002/cbin.11621
  60. Establishment of an in vitro thrombogenicity test system with cyclic olefin copolymer substrate for endothelial layer formation vol.11, pp.5, 2021, https://doi.org/10.1557/s43579-021-00072-6
  61. Relationship Between Coronary Atheroma, Epicardial Adipose Tissue Inflammation, and Adipocyte Differentiation Across the Human Myocardial Bridge vol.10, pp.22, 2014, https://doi.org/10.1161/jaha.121.021003
  62. Predicting the onset of consequent stenotic regions in carotid arteries using computational fluid dynamics vol.33, pp.12, 2021, https://doi.org/10.1063/5.0068998
  63. Cell membrane rupture: a novel test reveals significant variations among different brands of tissue culture flasks vol.14, pp.None, 2014, https://doi.org/10.1186/s13104-021-05453-7