Skip to main content
Log in

Impact of Bi-Axial Shear on Atherogenic Gene Expression by Endothelial Cells

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

An Erratum to this article was published on 22 June 2016

This article has been updated

Abstract

This study demonstrated the effects of the directionality of oscillatory wall shear stress (WSS) on proliferation and proatherogenic gene expression (I-CAM, E-Selectin, and IL-6) in the presence of inflammatory mediators leukotriene B4 (LTB4) and bacterial lipopolysaccharide (LPS) from endothelial cells grown in an orbiting culture dish. Computational fluid dynamics (CFD) was applied to quantify the flow in the dish, while an analytical solution representing an extension of Stokes second problem was used for validation. Results indicated that WSS magnitude was relatively constant near the center of the dish and oscillated significantly (0–0.9 Pa) near the side walls. Experiments showed that LTB4 dominated the shear effects on cell proliferation and area. Addition of LPS didn’t change proliferation, but significantly affected cell area. The expression of I-CAM1, E-Selectin and IL-6 were altered by directional oscillatory shear index (DOSI, a measure of the biaxiality of oscillatory shear), but not shear magnitude. The significance of DOSI was further reinforced by the strength of its interactions with other atherogenic factors. Hence, directionality of shear appears to be an important factor in regulating gene expression and provides a potential explanation of the propensity for increased vascular lesions in regions in the arteries with oscillating biaxial flow.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8

Similar content being viewed by others

Change history

  • 22 June 2016

    An erratum to this article has been published.

References

  1. Aiello, R. J., D. Brees, P. A. Bourassa, L. Royer, S. Lindsey, T. Coskran, M. Haghpassand, and O. L. Francone. Increased atherosclerosis in hyperlipidemic mice with inactivation of ABCA1 in macrophages. Arterioscler. Thromb. Vasc. Biol. 22:630–637, 2002.

    Article  CAS  PubMed  Google Scholar 

  2. Berson R. E., M. R. Purcell and M. K. Sharp. Computationally determined shear on cells grown in orbiting culture dishes. Adv. Exp. Med. Biol. 614:189–198, 2008.

    Article  PubMed  Google Scholar 

  3. Bourdillon, M. C., R. N. Poston, C. Covacho, E. Chignier, G. Bricca, and J. L. McGregor. ICAM-1 deficiency reduces atherosclerotic lesions in double-knockout mice (ApoE(-/-)/ICAM-1(-/-)) fed a fat or a chow diet. Arterioscler. Thromb. Vasc. Biol. 20:2630–2635, 2000.

    Article  CAS  PubMed  Google Scholar 

  4. Chakraborty, A., S. Chakraborty, V. R. Jala, B. Haribabu, M. K. Sharp, and R. E. Berson. Effects of biaxial oscillatory shear stress on endothelial cell proliferation and morphology. Biotechnol. Bioeng. 109:695–707, 2012.

    Article  CAS  PubMed  Google Scholar 

  5. Chappell, D. C., S. E. Varner, R. M. Nerem, R. M. Medford, and R. W. Alexander. Oscillatory shear stress stimulates adhesion molecule expression in cultured human endothelium. Circ. Res. 82:532–539, 1998.

    Article  CAS  PubMed  Google Scholar 

  6. Cunningham, K. S., and A. I. Gotlieb. The role of shear stress in the pathogenesis of atherosclerosis. Lab. Invest. 85:9–23, 2005.

    Article  CAS  PubMed  Google Scholar 

  7. Dahl, A., M. Sultan, A. Jung, R. Schwartz, M. Lange, M. Steinwand, K. J. Livak, H. Lehrach, and L. Nyarsik. Quantitative PCR based expression analysis on a nanoliter scale using polymer nano-well chips. Biomed. Microdevices 9:307–314, 2007.

    Article  CAS  PubMed  Google Scholar 

  8. Frank, P. G., and M. P. Lisanti. ICAM-1: role in inflammation and in the regulation of vascular permeability. Am. J. Physiol. Heart Circ. Physiol. 295:H926–H927, 2008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Fujihara, M., M. Muroi, K. Tanamoto, T. Suzuki, H. Azuma, and H. Ikeda. Molecular mechanisms of macrophage activation and deactivation by lipopolysaccharide: roles of the receptor complex. Pharmacol. Ther. 100:171–194, 2003.

    Article  CAS  PubMed  Google Scholar 

  10. Galkina, E., and K. Ley. Vascular adhesion molecules in atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 27:2292–2301, 2007.

    Article  CAS  PubMed  Google Scholar 

  11. Inoguchi, H., T. Tanaka, Y. Maehara, and T. Matsuda. The effect of gradually graded shear stress on the morphological integrity of a huvec-seeded compliant small-diameter vascular graft. Biomaterials 28:486–495, 2007.

    Article  CAS  PubMed  Google Scholar 

  12. Ku, D. N., D. P. Giddens, C. K. Zarins, and S. Glagov. Pulsatile flow and atherosclerosis in the human carotid bifurcation. Positive correlation between plaque location and low oscillating shear stress. Arteriosclerosis 5:293–302, 1985.

    Article  CAS  PubMed  Google Scholar 

  13. Levesque, M. J., and R. M. Nerem. The elongation and orientation of cultured endothelial cells in response to shear stress. J. Biomech. Eng. 107:341–347, 1985.

    Article  CAS  PubMed  Google Scholar 

  14. Libby, P. Inflammation in atherosclerosis. Nature 420:868–874, 2002.

    Article  CAS  PubMed  Google Scholar 

  15. Mehrabian, M., H. Allayee, J. Wong, W. Shi, X. P. Wang, Z. Shaposhnik, C. D. Funk, and A. J. Lusis. Identification of 5-lipoxygenase as a major gene contributing to atherosclerosis susceptibility in mice. Circ. Res. 91:120–126, 2002.

    Article  CAS  PubMed  Google Scholar 

  16. Mehrabian, M., J. Wong, X. Wang, Z. Jiang, W. Shi, A. M. Fogelman, and A. J. Lusis. Genetic locus in mice that blocks development of atherosclerosis despite extreme hyperlipidemia. Circ. Res. 89:125–130, 2001.

    Article  CAS  PubMed  Google Scholar 

  17. Nakashima, Y., E. W. Raines, A. S. Plump, J. L. Breslow, and R. Ross. Upregulation of VCAM-1 and ICAM-1 at atherosclerosis-prone sites on the endothelium in the ApoE-deficient mouse. Arterioscler. Thromb. Vasc. Biol. 18:842–851, 1998.

    Article  CAS  PubMed  Google Scholar 

  18. Nerem, R. M., M. J. Levesque, and J. F. Cornhill. Vascular endothelial morphology as an indicator of the pattern of blood flow. J. Biomech. Eng. 103:172–176, 1981.

    Article  CAS  PubMed  Google Scholar 

  19. Owatverot, T. B., S. J. Oswald, Y. Chen, J. J. Wille, and F. C. Yin. Effect of combined cyclic stretch and fluid shear stress on endothelial cell morphological responses. J. Biomech. Eng. 127:374–382, 2005.

    Article  PubMed  Google Scholar 

  20. Pfenniger, A., M. J. Meens, R. M. Pedrigi, B. Foglia, E. Sutter, G. Pelli, V. Rochemont, T. V. Petrova, R. Krams, and B. R. Kwak. Shear stress-induced atherosclerotic plaque composition in ApoE(-/-) mice is modulated by connexin37. Atherosclerosis 243:1–10, 2015.

    Article  CAS  PubMed  Google Scholar 

  21. Ridger, V., R. Krams, A. Carpi, and P. C. Evans. Hemodynamic parameters regulating vascular inflammation and atherosclerosis: a brief update. Biomed. Pharmacother. 62:536–540, 2008.

    Article  CAS  PubMed  Google Scholar 

  22. Ross, R. Atherosclerosis is an inflammatory disease. Am. Heart J. 138:S419–S420, 1999.

    Article  CAS  PubMed  Google Scholar 

  23. Sawa, Y., T. Ueki, M. Hata, K. Iwasawa, E. Tsuruga, H. Kojima, H. Ishikawa, and S. Yoshida. LPS-induced IL-6, IL-8, VCAM-1, and ICAM-1 expression in human lymphatic endothelium. J. Histochem. Cytochem. 56:97–109, 2008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Schieffer, B., T. Selle, A. Hilfiker, D. Hilfiker-Kleiner, K. Grote, U. J. Tietge, C. Trautwein, M. Luchtefeld, C. Schmittkamp, S. Heeneman, M. J. Daemen, and H. Drexler. Impact of interleukin-6 on plaque development and morphology in experimental atherosclerosis. Circulation 110:3493–3500, 2004.

    Article  CAS  PubMed  Google Scholar 

  25. Schuett, H., M. Luchtefeld, C. Grothusen, K. Grote, and B. Schieffer. How much is too much? Interleukin-6 and its signalling in atherosclerosis. Thromb. Haemost. 102:215–222, 2009.

    CAS  PubMed  Google Scholar 

  26. Sukovich, D. A., K. Kauser, F. D. Shirley, V. DelVecchio, M. Halks-Miller, and G. M. Rubanyi. Expression of interleukin-6 in atherosclerotic lesions of male ApoE-knockout mice: inhibition by 17beta-estradiol. Arterioscler. Thromb. Vasc. Biol. 18:1498–1505, 1998.

    Article  CAS  PubMed  Google Scholar 

  27. Sumagin, R., E. Lomakina, and I. H. Sarelius. Leukocyte-endothelial cell interactions are linked to vascular permeability via ICAM-1-mediated signaling. Am. J. Physiol. Heart Circ. Physiol. 295:H969–H977, 2008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Thomas, J. M., A. Chakraborty, M. K. Sharp, and R. E. Berson. Spatial and temporal resolution of shear in an orbiting petri dish. Biotechnol. Prog. 27:460–465, 2011.

    Article  CAS  PubMed  Google Scholar 

  29. VanderLaan, P. A., C. A. Reardon, and G. S. Getz. Site specificity of atherosclerosis: site-selective responses to atherosclerotic modulators. Arterioscler. Thromb. Vasc. Biol. 24:12–22, 2004.

    Article  CAS  PubMed  Google Scholar 

  30. Venables, W. N., and B. D. Ripley. Modern Applied Statistics with S. New York: Springer, 2002.

    Book  Google Scholar 

  31. Yamaguchi, T., Y. Yamamoto, and H. Liu. Computational mechanical model studies on the spontaneous emergent morphogenesis of the cultured endothelial cells. J. Biomech. 33:115–126, 2000.

    Article  CAS  PubMed  Google Scholar 

  32. Zhou, J., Y. S. Li, and S. Chien. Shear stress-initiated signaling and its regulation of endothelial function. Arterioscler. Thromb. Vasc. Biol. 34:2191–2198, 2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to R. Eric Berson or Bodduluri Haribabu.

Additional information

Associate Editor Kerry Hourigan oversaw the review of this article.

An erratum to this article is available at https://doi.org/10.1007/s10439-016-1665-8.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chakraborty, A., Chakraborty, S., Jala, V.R. et al. Impact of Bi-Axial Shear on Atherogenic Gene Expression by Endothelial Cells. Ann Biomed Eng 44, 3032–3045 (2016). https://doi.org/10.1007/s10439-016-1626-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-016-1626-2

Keywords

Navigation