Advertisement

Annals of Biomedical Engineering

, Volume 38, Issue 5, pp 1880–1892 | Cite as

HUVEC ICAM-1 and VCAM-1 Synthesis in Response to Potentially Athero-Prone and Athero-Protective Mechanical and Nicotine Chemical Stimuli

  • Liam T. BreenEmail author
  • Peter E. McHugh
  • Bruce P. Murphy
Article

Abstract

Previous mechano-transduction studies have investigated the endothelial cell (EC) morphological response to mechanical stimuli; generally consisting of a wall shear stress (WSS) and a cyclic tensile hoop strain (THS). More recent studies have investigated the EC biochemical response (intercellular adhesion molecule, ICAM-1, and vascular cellular adhesion molecule, VCAM-1, expression) to idealized mechanical stimuli. However, current literature is lacking in the area of EC biochemical response to combinations of physiological WSS and THS mechanical stimuli. The objective of this study is to investigate the EC response to physiological WSS and THS stimuli and to compare this response to that of ECs exposed to idealized steady WSS and cyclic THS of the same magnitudes. This study also investigated the EC response to a nicotine chemical stimulus combined with a suspected athero-prone physiological mechanical stimulus. A bioreactor was designed to apply a range of combinations of physiological WSS and THS waveforms. The bioreactor was calibrated and validated using computational fluid dynamics and video extensometry techniques. The bioreactor was used to investigated the biochemical response exhibited by human umbilical vein endothelial cells (HUVECs) exposed to physiological athero-protective (first bioreactor test case, pulsatile WSS combined with pulsatile THS) and athero-prone (second bioreactor test case, oscillating WSS combined with pulsatile THS) mechanical environments. The final testing environment (third bioreactor test case) combined a nicotine chemical stimulus with the mechanical stimuli of the second bioreactor test case. In first and second bioreactor test cases, the addition of a pulsatile THS to the WSS resulted in opposite trends of ICAM-1 down-regulation and up-regulation, respectively. This outcome suggests that the effect of the additional pulsatile THS depends on the state of the applied WSS waveform. Similarly, in first and second bioreactor test cases, the addition of a pulsatile THS to the WSS resulted in a VCAM-1 up-regulation. However, it has been previously shown that the addition of a cyclic THS to a high- or low-steady WSS resulted in a VCAM-1 down-regulation, indicating that the EC response to idealized mechanical stimuli (steady WSS and cyclic THS) is not comparable to physiological mechanical stimuli (unsteady WSS and pulsatile THS), even though in both situations the average magnitude of WSS and THS applied were similar. In third bioreactor test case, a nicotine chemical stimulus induced a substantial VCAM-1 up-regulation and a moderate ICAM-1 up-regulation. The addition of the mechanical stimuli of the second bioreactors test case resulted in a greater VCAM-1 up-regulation than what was expected, considering the observations of the previous second bioreactor test case alone. This study found that the EC biochemical response to physiological mechanical stimuli is not comparable to the previously observed EC response to idealized mechanical stimuli, even though in both environments the mechanical stimuli were of a similar magnitude. Also, the level of VCAM-1 expressed by the nicotine stimulated ECs showed an elevated level of sensitivity to the athero-prone mechanical stimuli.

Keywords

Cell mechanotransduction Wall shear stress Tensile hoop stretch ICAM-1 VCAM-1 Nicotine 

Notes

Acknowledgments

The authors acknowledge support from the Program for Research in Third Level Institutions (PRTLI), administered by the Higher Education Authority (HEA). The project was carried out at the National Centre for Biomedical Engineering Science (NCBES), National University of Ireland, Galway, in association with University of Limerick, and Institute of Technology, Sligo. L. Breen acknowledges funding from the Irish Research Council for Science, Engineering and Technology (IRCSET) under the Embark Initiative Postgraduate Research Scholarship Scheme.

References

  1. 1.
    Albaugh, G., et al. Nicotine induces mononuclear leukocyte adhesion and expression of adhesion molecules, VCAM and ICAM, in endothelial cells in vitro. Ann. Vasc. Surg. 18(3):302–307, 2004.CrossRefPubMedGoogle Scholar
  2. 2.
    Ali, M. H., et al. Mitochondrial requirement for endothelial responses to cyclic strain: implications for mechanotransduction. Am. J. Physiol. Lung Cell Mol. Physiol. 287(3):L486–L496, 2004.CrossRefPubMedGoogle Scholar
  3. 3.
    Ando, J., et al. Shear stress inhibits adhesion of cultured mouse endothelial cells to lymphocytes by downregulating VCAM-1 expression. Am. J. Physiol. 267(3 Pt 1):C679–C687, 1994.PubMedGoogle Scholar
  4. 4.
    Barakat, A., and D. Lieu. Differential responsiveness of vascular endothelial cells to different types of fluid mechanical shear stress. Cell Biochem. Biophys. 38(3):323–343, 2003.CrossRefPubMedGoogle Scholar
  5. 5.
    Benowitz, N. L., et al. Interindividual variability in the metabolism and cardiovascular effects of nicotine in man. J. Pharmacol. Exp. Ther. 221(2):368–372, 1982.PubMedGoogle Scholar
  6. 6.
    Blackman, B. R., K. A. Barbee, and L. E. Thibault. In vitro cell shearing device to investigate the dynamic response of cells in a controlled hydrodynamic environment. Ann. Biomed. Eng. 28:363–372, 2000.CrossRefPubMedGoogle Scholar
  7. 7.
    Blackman, B. R., G. Garcia-Cardena, and M. A. Gimbrone, Jr. A new in vitro model to evaluate differential responses of endothelial cells to simulated arterial shear stress waveforms. J. Biomech. Eng. 124(4):397–407, 2002.CrossRefPubMedGoogle Scholar
  8. 8.
    Breen, L., P. E. McHugh, B. P. Murphy, et al. Multi-axial mechanical stimulation of HUVECs demonstrates that combined loading is not equivalent to the superposition of individual wall shear stress and tensile hoop stress components. J. Biomech. Eng. 131(8):081001, 2009.CrossRefPubMedGoogle Scholar
  9. 9.
    Breen, L., et al. Development of a novel bioreactor to apply shear stress and tensile strain simultaneously to cell monolayers. Rev. Sci. Instrum. 77:104301, 2006.CrossRefGoogle Scholar
  10. 10.
    Brooks, A. R., P. I. Lelkes, and G. M. Rubanyi. Gene expression profiling of human aortic endothelial cells exposed to disturbed flow and steady laminar flow. Physiol. Genom. 9(1):27–41, 2002.Google Scholar
  11. 11.
    Buck, R. C. Reorientation response of cells to repeated stretch and recoil of the substratum. Exp. Cell Res. 127(2):470–474, 1980.CrossRefPubMedGoogle Scholar
  12. 12.
    Buschmann, M. H., et al. Analysis of flow in a cone-and-plate apparatus with respect to spatial and temporal effects on endothelial cells. Biotechnol. Bioeng. 89:493–502, 2002.CrossRefGoogle Scholar
  13. 13.
    Bussolari, S. R., C. F. Dewey, Jr., and M. A. Gimbrone, Jr. Apparatus for subjecting living cells to fluid shear stress. Rev. Sci. Instrum. 53(12):1851–1854, 1982.CrossRefPubMedGoogle Scholar
  14. 14.
    Chappell, D. C., et al. Oscillatory shear stress stimulates adhesion molecule expression in cultured human endothelium. Circ. Res. 82(5):532–539, 1998.PubMedGoogle Scholar
  15. 15.
    Cheng, J. J., et al. Cyclic strain enhances adhesion of monocytes to endothelial cells by increasing intercellular adhesion molecule-1 expression. Hypertension 28(3):386–391, 1996.PubMedGoogle Scholar
  16. 16.
    Chiu, J. J., et al. Shear stress inhibits adhesion molecule expression in vascular endothelial cells induced by coculture with smooth muscle cells. Blood 101(7):2667–2674, 2003.CrossRefPubMedGoogle Scholar
  17. 17.
    Chiu, J. J., et al. Shear stress increases ICAM-1 and decreases VCAM-1 and E-selectin expressions induced by tumor necrosis factor-[alpha] in endothelial cells. Arterioscler. Thromb. Vasc. Biol. 24(1):73–79, 2004.CrossRefPubMedGoogle Scholar
  18. 18.
    Clark, C. B., T. J. Burkholder, and J. A. Frangos. Uniaxial strain system to investigate strain rate regulation in vitro. Rev. Sci. Instrum. 72:2415–2422, 2001.CrossRefGoogle Scholar
  19. 19.
    Dai, G., et al. Distinct endothelial phenotypes evoked by arterial waveforms derived from atherosclerosis-susceptible and -resistant regions of human vasculature. Proc. Natl. Acad. Sci. USA 101(41):14871–14876, 2004.CrossRefPubMedGoogle Scholar
  20. 20.
    Dartsch, P. C., and E. Betz. Response of cultured endothelial cells to mechanical stimulation. Basic Res. Cardiol. 84(3):268–281, 1989.CrossRefPubMedGoogle Scholar
  21. 21.
    Dewey, Jr., C. F., et al. The dynamic response of vascular endothelial cells to fluid shear stress. J. Biomech. Eng. 103(3):177–185, 1981.CrossRefPubMedGoogle Scholar
  22. 22.
    Frijns, C. J., and L. J. Kappelle. Inflammatory cell adhesion molecules in ischemic cerebrovascular disease. Stroke 33(8):2115–2122, 2002.CrossRefPubMedGoogle Scholar
  23. 23.
    Gnasso, A., et al. In vivo association between low wall shear stress and plaque in subjects with asymmetrical carotid atherosclerosis. Stroke 28(5):993–998, 1997.PubMedGoogle Scholar
  24. 24.
    He, X., and D. N. Ku. Pulsatile flow in the human left coronary artery bifurcation: average conditions. J. Biomech. Eng. 118(1):74–82, 1996.CrossRefPubMedGoogle Scholar
  25. 25.
    Hoffmann, R., et al. Patterns and Mechanisms of In-Stent Restenosis: A Serial Intravascular Ultrasound Study. Circulation 94(6):1247–1254, 1996.PubMedGoogle Scholar
  26. 26.
    Hsiai, T. K., et al. Monocyte recruitment to endothelial cells in response to oscillatory shear stress. Faseb. J. 17(12):1648–1657, 2003.CrossRefPubMedGoogle Scholar
  27. 27.
    Kanda, K., and T. Matsuda. Behavior of arterial wall cells cultured on periodically stretched substrates. Cell Transpl. 2(6):475–484, 1993.Google Scholar
  28. 28.
    Malek, A. M., S. L. Alper, and S. Izumo. Hemodynamic shear stress and its role in atherosclerosis. JAMA 282(21):2035–2042, 1999.CrossRefPubMedGoogle Scholar
  29. 29.
    Mohan, S., et al. Regulation of low shear flow-induced HAEC VCAM-1 expression and monocyte adhesion. Am. J. Physiol. 276(5 Pt 1):C1100–C1107, 1999.PubMedGoogle Scholar
  30. 30.
    Moore, Jr., J. E., et al. A device for subjecting vascular endothelial cells to both fluid shear stress and circumferential cyclic stretch. Ann. Biomed. Eng. 22(4):416–422, 1994.CrossRefPubMedGoogle Scholar
  31. 31.
    Moretti, M., et al. Endothelial cell alignment on cyclically-stretched silicone surfaces. J. Mater. Sci. Mater. Med. 15(10):1159–1164, 2004.CrossRefPubMedGoogle Scholar
  32. 32.
    Morigi, M., et al. Fluid shear stress modulates surface expression of adhesion molecules by endothelial cells. Blood 85(7):1696–1703, 1995.PubMedGoogle Scholar
  33. 33.
    Nagel, T., et al. Shear stress selectively upregulates intercellular adhesion molecule-1 expression in cultured human vascular endothelial cells. J. Clin. Invest. 94(2):885–891, 1994.CrossRefPubMedGoogle Scholar
  34. 34.
    Naruse, K., T. Yamada, and M. Sokabe. Involvement of SA channels in orienting response of cultured endothelial cells to cyclic stretch. Am. J. Physiol. Heart Circ. 274:H1532–H1538, 1998.Google Scholar
  35. 35.
    Neidlinger-Wilke, C., et al. Cell alignment is induced by cyclic changes in cell length: studies of cells grown in cyclically stretched substrates. J. Orthop. Res. 19(2):286–293, 2001.CrossRefPubMedGoogle Scholar
  36. 36.
    Ohtsuka, A., et al. The effect of flow on the expression of vascular adhesion molecule-1 by cultured mouse endothelial cells. Biochem. Biophys. Res. Commun. 193(1):303–310, 1993.CrossRefPubMedGoogle Scholar
  37. 37.
    Qiu, Y., and J. M. Tarbell. Interaction between wall shear stress and circumferential strain affects endothelial cell biochemical production. J. Vasc. Res. 37(3):147–157, 2000.CrossRefPubMedGoogle Scholar
  38. 38.
    Sato, M., N. Ohshima, and R. M. Nerem. Viscoelastic properties of cultured porcine aortic endothelial cells exposed to shear stress. J. Biomech. 29(4):461–467, 1996.CrossRefPubMedGoogle Scholar
  39. 39.
    Shirinsky, V. P., et al. Mechano-chemical control of human endothelium orientation and size. J. Cell Biol. 109(1):331–339, 1989.CrossRefPubMedGoogle Scholar
  40. 40.
    Sipkema, P., et al. Effect of cyclic axial stretch of rat arteries on endothelial cytoskeletal morphology and vascular reactivity. J. Biomech. 36(5):653–659, 2003.CrossRefPubMedGoogle Scholar
  41. 41.
    Smith, B. W., et al. Velocity profile method for time varying resistance in minimal cardiovascular system models. Phys. Med. Biol. 48(20):3375–3387, 2003.CrossRefPubMedGoogle Scholar
  42. 42.
    Takemasa, T., et al. Oblique alignment of stress fibers in cells reduces the mechanical stress in cyclically deforming fields. Eur. J. Cell Biol. 77(2):91–99, 1998.PubMedGoogle Scholar
  43. 43.
    Tsao, P. S., et al. Fluid flow inhibits endothelial adhesiveness. Nitric oxide and transcriptional regulation of VCAM-1. Circulation 94(7):1682–1689, 1996.PubMedGoogle Scholar
  44. 44.
    Wang, J. H., P. Goldschmidt-Clermont, and F. C. Yin. Contractility affects stress fiber remodeling and reorientation of endothelial cells subjected to cyclic mechanical stretching. Ann. Biomed. Eng. 28(10):1165–1171, 2000.CrossRefPubMedGoogle Scholar
  45. 45.
    Wang, D. L., et al. Cyclical strain increases endothelin-1 secretion and gene expression in human endothelial cells. Biochem. Biophys. Res. Commun. 195(2):1050–1056, 1993.CrossRefPubMedGoogle Scholar
  46. 46.
    Wang, H., et al. Cell orientation response to cyclically deformed substrates: experimental validation of a cell model. J. Biomech. 28(12):1543–1552, 1995.CrossRefPubMedGoogle Scholar
  47. 47.
    Wang, J. H., et al. Specificity of endothelial cell reorientation in response to cyclic mechanical stretching. J. Biomech. 34(12):1563–1572, 2001.CrossRefPubMedGoogle Scholar
  48. 48.
    Wang, J. H., et al. Fibroblast responses to cyclic mechanical stretching depend on cell orientation to the stretching direction. J. Biomech. 37(4):573–576, 2004.CrossRefPubMedGoogle Scholar
  49. 49.
    Yun, J. K., J. M. Anderson, and N. P. Ziats. Cyclic-strain-induced endothelial cell expression of adhesion molecules and their roles in monocyte–endothelial interaction. J. Biomed. Mater. Res. 44(1):87–97, 1999.CrossRefPubMedGoogle Scholar
  50. 50.
    Zarins, C. K., et al. Carotid bifurcation atherosclerosis. Quantitative correlation of plaque localization with flow velocity profiles and wall shear stress. Circ. Res. 53(4):502–514, 1983.PubMedGoogle Scholar
  51. 51.
    Zhang, S., I. Day, and S. Ye. Nicotine induced changes in gene expression by human coronary artery endothelial cells. Atherosclerosis 154(2):277–283, 2001.CrossRefPubMedGoogle Scholar
  52. 52.
    Zhao, S., et al. Synergistic effects of fluid shear stress and cyclic circumferential stretch on vascular endothelial cell morphology and cytoskeleton. Arterioscler. Thromb. Vasc. Biol. 15(10):1781–1786, 1995.PubMedGoogle Scholar
  53. 53.
    Zhao, S. Z., et al. Inter-individual variations in wall shear stress and mechanical stress distributions at the carotid artery bifurcation of healthy humans. J. Biomech. 35(10):1367–1377, 2002.CrossRefPubMedGoogle Scholar

Copyright information

© Biomedical Engineering Society 2010

Authors and Affiliations

  • Liam T. Breen
    • 1
    • 2
    • 3
    Email author
  • Peter E. McHugh
    • 1
    • 2
  • Bruce P. Murphy
    • 1
  1. 1.National Centre for Biomedical Engineering ScienceNational University of Ireland GalwayGalwayIreland
  2. 2.Department of Mechanical and Biomedical EngineeringNational University of IrelandGalwayIreland
  3. 3.Department of Mechanical and Manufacturing EngineeringParsons Building, Trinity College DublinDublin 2Ireland

Personalised recommendations