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Correlation of Hemodynamic Parameters to Endothelial Cell Proliferation in an End to Side Anastomosis

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Abstract

A strong correlation between the localization of atherosclerotic lesions with abnormal wall shear stress (WSS) has long been recognized at the distal anastomosis of a peripheral bypass where disturbed flow occurs. Identification of a WSS variable that significantly contributes to disease formation at this site has been elusive to date, as endothelial cell (EC) response to the abnormal hemodynamics at this anastomotic junction has yet to be quantitatively characterized. In vitro experiments were performed exposing human aortic ECs to pulsatile flow variables appropriate to a distal bypass graft junction using a novel in vitro device. Computational fluid dynamics was employed to detail the hemodynamic variables of this flow chamber. These variables were then correlated to EC proliferation which was used as an indicator of intimal hyperplasia (IH) development. Under pulsatile flow, maximum absolute temporal WSS gradient was found to be the parameter that most significantly correlated to EC proliferation (p = 0.0001, r = 0.8947). This metric can be utilized as an indicator to detect arterial segments prone to the initiation and localization of IH, it may also be used to help optimize the surgical construction of coronary artery bypass, peripheral bypass and arteriovenous anastomotic junctions to improve patient outcomes.

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References

  1. Bao, X., C. B. Clark, and J. A. Frangos. Temporal gradient in shear-induced signaling pathway: involvement of MAP kinase, c-fos, and connexin43. Am. J. Physiol. Heart Circ. Physiol. 278:H1598–H1605, 2000.

    Google Scholar 

  2. Bao, X., C. Lu, and J. A. Frangos. Temporal gradient in shear but not steady shear stress induces PDGF-A and MCP-1 expression in endothelial cells: role of NO, NF B, and egr-1. Arterioscler. Thromb. Vasc. Biol. 19:996–1003, 1999.

    Article  Google Scholar 

  3. Barbee, K. Role of subcellular shear–stress distributions in endothelial cell mechanotransduction. Ann. Biomed. Eng. 30:472–482, 2002.

    Article  Google Scholar 

  4. Bassiouny, H. S., S. White, S. Glagov, E. Choi, D. P. Giddens, and C. K. Zarins. Anastomotic intimal hyperplasia: mechanical injury or flow induced. J. Vasc. Surg. 15:708–717, 1992.

    Article  Google Scholar 

  5. Chatzizisis, Y. S., A. U. Coskun, M. Jonas, E. R. Edelman, C. L. Feldman, and P. H. Stone. Role of endothelial shear stress in the natural history of coronary atherosclerosis and vascular remodeling: molecular, cellular, and vascular behavior. J. Am. Coll. Cardiol. 49:2379–2393, 2007.

    Article  Google Scholar 

  6. Chien, S. Molecular and mechanical bases of focal lipid accumulation in arterial wall. Prog. Biophys. Mol. Biol. 83:131–151, 2003.

    Article  Google Scholar 

  7. Haidekker, M. A., C. R. White, and J. A. Frangos. Analysis of temporal shear stress gradients during the onset phase of flow over a backward-facing step. J. Biomech. Eng. 123:455, 2001.

    Article  Google Scholar 

  8. Haruguchi, H., and S. Teraoka. Intimal hyperplasia and hemodynamic factors in arterial bypass and arteriovenous grafts: a review. J. Artif. Organs 6:227–235, 2003.

    Article  Google Scholar 

  9. Hofer, M., G. Rappitsch, K. Perktold, W. Trubel, and H. Schima. Numerical study of wall mechanics and fluid dynamics in end-to-side anastomoses and correlation to intimal hyperplasia. J. Biomech. 29:1297–1308, 1996.

    Article  Google Scholar 

  10. Keynton, R. S., M. M. Evancho, R. L. Sims, N. V. Rodway, A. Gobin, and S. E. Rittgers. Intimal hyperplasia and wall shear in arterial bypass graft distal anastomoses: an in vivo model study. J. Biomech. Eng. 123:464–473, 2001.

    Article  Google Scholar 

  11. Klein, W. M., L. W. Bartels, L. Bax, Y. van der Graaf, and W. P. T. M. Mali. Magnetic resonance imaging measurement of blood volume flow in peripheral arteries in healthy subjects. J. Vasc. Surg. 38:1060–1066, 2003.

    Article  Google Scholar 

  12. Kornet, L., A. P. G. Hoeks, J. Lambregts, and R. S. Reneman. In the femoral artery bifurcation, differences in mean wall shear stress within subjects are associated with different intima-media thicknesses. Arterioscler. Thromb. Vasc. Biol. 19:2933–2939, 1999.

    Article  Google Scholar 

  13. 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. Arterioscler. Thromb. Vasc. Biol. 5:293–302, 1985.

    Article  Google Scholar 

  14. Kute, S. M., and D. A. Vorp. The effect of proximal artery flow on the hemodynamics at the distal anastomosis of a vascular bypass graft: computational study. J. Biomech. Eng. 123:277, 2001.

    Article  Google Scholar 

  15. Lei, M., J. P. Archie, and C. Kleinstreuer. Computational design of a bypass graft that minimizes wall shear stress gradients in the region of the distal anastomosis. J. Vasc. Surg. 25:637–646, 1997.

    Article  Google Scholar 

  16. Li, Y.-S. J., J. H. Haga, and S. Chien. Molecular basis of the effects of shear stress on vascular endothelial cells. J. Biomech. 38:1949–1971, 2005.

    Article  Google Scholar 

  17. Longest, P. W., and C. Kleinstreuer. Particle-hemodynamics modeling of the distal end-to-side femoral bypass: effects of graft caliber and graft-end cut. Med. Eng. Phys. 25:843–858, 2003.

    Article  Google Scholar 

  18. Michiels, C. Endothelial cell functions. J. Cell. Physiol. 196:430–443, 2003.

    Article  Google Scholar 

  19. Nagel, T., N. Resnick, C. F. Dewey, and M. A. Gimbrone. Vascular endothelial cells respond to spatial gradients in fluid shear stress by enhanced activation of transcription factors. Arterioscler. Thromb. Vasc. Biol. 19:1825–1834, 1999.

    Article  Google Scholar 

  20. O’Brien, T., M. Walsh, and T. McGloughlin. Altering end-to-side anastomosis junction hemodynamics: the effects of flow-splitting. Med. Eng. Phys. 28:727–733, 2006.

    Article  Google Scholar 

  21. Ojha, M. Wall shear stress temporal gradient and anastomotic intimal hyperplasia. Circ. Res. 74:1227–1231, 1994.

    Article  Google Scholar 

  22. Passerini, A. G., A. Milsted, and S. E. Rittgers. Shear stress magnitude and directionality modulate growth factor gene expression in preconditioned vascular endothelial cells. J. Vasc. Surg. 37:182–190, 2003.

    Article  Google Scholar 

  23. Perktold, K., A. Leuprecht, M. Prosi, T. Berk, M. Czerny, W. Trubel, and H. Schima. Fluid dynamics, wall mechanics, and oxygen transfer in peripheral bypass anastomoses. Ann. Biomed. Eng. 30:447–460, 2002.

    Article  Google Scholar 

  24. Tardy, Y., N. Resnick, T. Nagel, M. A. Gimbrone, and C. F. Dewey. Shear stress gradients remodel endothelial monolayers in vitro via a cell proliferation–migration–loss cycle. Arterioscler. Thromb. Vasc. Biol. 17:3102–3106, 1997.

    Article  Google Scholar 

  25. Walsh, M. T., E. G. Kavanagh, T. O’Brien, P. A. Grace, and T. McGloughlin. On the existence of an optimum end-to-side junctional geometry in peripheral bypass surgery–a computer generated study. Eur. J. Vasc. Endovasc. Surg. 26:649–656, 2003.

    Article  Google Scholar 

  26. White, C. R., and J. A. Frangos. The shear stress of it all: the cell membrane and mechanochemical transduction. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 362:1459–1467, 2007.

    Article  Google Scholar 

  27. White, C. R., M. Haidekker, X. Bao, and J. A. Frangos. Temporal gradients in shear, but not spatial gradients, stimulate endothelial cell proliferation. Circulation 103:2508–2513, 2001.

    Article  Google Scholar 

  28. White, C. R., H. Y. Stevens, M. Haidekker, and J. A. Frangos. Temporal gradients in shear, but not spatial gradients, stimulate ERK1/2 activation in human endothelial cells. Am. J. Physiol. Heart Circ. Physiol. 289:2350–2355, 2005.

    Article  Google Scholar 

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Acknowledgments

The author would like to acknowledge Enterprise Ireland, The Irish Research Council for Science Engineering and Technology (IRCSET) and the Nerem Laboratory at the Institute for Bioengineering and Bioscience at Georgia Institute of Technology.

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All authors declare that they have no conflict of interest.

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No human studies were carried out by the authors for this article. No animal studies were carried out by the authors for this article.

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Authors and Affiliations

  1. Department of Mechanical, Aeronautical & Biomedical Engineering, Centre for Applied Biomedical Engineering Research (CABER), Materials and Surface Science Institute, University of Limerick, Limerick, Ireland

    Leonard D. Browne, Siobhan O’Callaghan, David A. Hoey, Philip Griffin, Timothy M. McGloughlin & Michael T. Walsh

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  1. Leonard D. Browne
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  2. Siobhan O’Callaghan
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  3. David A. Hoey
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  4. Philip Griffin
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  5. Timothy M. McGloughlin
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  6. Michael T. Walsh
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Correspondence to Michael T. Walsh.

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Associate Editor Ajit P. Yoganathan oversaw the review of this article.

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Browne, L.D., O’Callaghan, S., Hoey, D.A. et al. Correlation of Hemodynamic Parameters to Endothelial Cell Proliferation in an End to Side Anastomosis. Cardiovasc Eng Tech 5, 110–118 (2014). https://doi.org/10.1007/s13239-013-0172-4

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  • DOI: https://doi.org/10.1007/s13239-013-0172-4

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