How Does the Arterial Endothelium Sense Flow? Hemodynamic Forces and Signal Transduction

  • Peter F. Davies
  • Randal O. Dull
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 273)


The focal nature of atherosclerotic lesions is associated with patterns of altered blood flow in the major arteries (1–3), although the precise nature of the flow in such regions is unclear. At the interface between flowing blood and the arterial wall, a confluent monolayer of endothelial cells operates as a signal-transduction system for hemodynamic forces associated with flow. Investigations of the influence of pressure, stretch and shear stress upon endothelial biology have therefore been conducted with a view to linking the precise flow profiles and the vessel wall pathophysiology. It is now clear that early atherogenesis develops in the presence of an intact endothelial monolayer (4–6, 10) consistent with the pivotal role that the endothelium may play in this disease process. The mechanisms by which physical forces influence endothelial biology, however, have yet to be fully defined.


Shear Stress Wall Shear Stress Pulsatile Flow Fluid Shear Stress Shear Stress Level 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    C.G. Caro, J.M. Fitzgerald, and R.C. Schroter, Atheroma and arterial wall shear, Observation, correlation and proposal of a shear dependent mass transfer mechanism for atherogenesis, Proc R Soc Lond B Biol Sci 177:109–159 (1971).PubMedCrossRefGoogle Scholar
  2. 2.
    J.T. Flaherty, V.J. Ferrans, J.E. Pierce, T.E. Carew, III, and D.L. Fry, Localizing factors in experimental atherosclerosis. In: “Atherosclerosis and Coronary Heart Disease”, pp. 40–83. W. Likoff, B.L. Segal, W. Insull, and S.J. Moyer, eds. Grune and Stratton. (1972).Google Scholar
  3. 3.
    J.F. Cornhill and M.R. Roach, A quantitative study of the localization of atherosclerotic lesions in the rabbit aorta, Atherosclerosis 23:489 (1976).PubMedCrossRefGoogle Scholar
  4. 4.
    P.F. Davies, M.A. Reidy, T.B. Goode, and D.E. Bowyer, Scanning electron microscopy in the evaluation of endothelial integrity of the fatty streak lesion of atherosclerosis. Atherosclerosis 25:125–130 (1976).PubMedCrossRefGoogle Scholar
  5. 5.
    T.B. Goode, P.F. Davies, M.A. Reidy, and D.E. Bowyer, Aortic endothelial cell morphology observed in situ by scanning electron microscopy during atherogenesis in the rabbit, Atherosclerosis 27:235–251 (1977).PubMedCrossRefGoogle Scholar
  6. 6.
    A. Faggiotto, R. Ross, and L. Harker, Studies of hypercholesterolemia in the non-human primate, I. Changes that lead to fatty streak formation, Arteriosclerosis 4:323 (1984).PubMedCrossRefGoogle Scholar
  7. 7.
    D.L. Fry, Acute vascular endothelial changes associated with increased blood velocity gradients, Circ Res 22:165–197 (1968).PubMedGoogle Scholar
  8. 8.
    D.L. Fry, Response of the arterial wall to certain physical factors, Ciba Found Symp 12:93–110 (1972).Google Scholar
  9. 9.
    C.K. Zarins, D.P. Giddens, B.K. Bharadvaj, V.S. Sottiurai, R.F. Mabon, and S. Glagov, Carotid bifurcation atherosclerosis. Quantitative correlation of plaque localization with flow velocity profiles and wall shear stress, Circ Res 53:502–514 (1983).PubMedGoogle Scholar
  10. 10.
    D.N. Ku, 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 and oscillating shear stress, Arteriosclerosis 5:293–301 (1985).PubMedCrossRefGoogle Scholar
  11. 11.
    S. Glagov, C.K. Zarins, K.E. Taylor, R.A. Bomberger, and D.P. Giddens, Evidence that high flow velocity and endothelial disruption are not the prinicipal factors in experimental plaque localization. In: “Fluid Dynamics as a Localizing Factor for Atherosclerosis”, pp. 208–211, G. Schettler, R.M. Nerem, H. Schmid-Schonbein and H. Morl, ed., Springer, Berlin (1983).Google Scholar
  12. 12.
    P.F. Davies, A. Remuzzi, E.J. Gordon, C.F. Dewey, and M.A. Gimbrone, Turbulent fluid shear stress induces vascular endothelial cell turnover in vitro, Proc Natl Acad Sci USA 83:2114–2117 (1986).PubMedCrossRefGoogle Scholar
  13. 13.
    T. Karino, M. Motomiya, and H.L. Goldsmith, Flow Patterns in Model and Natural Branching Vessels, in: “Fluid Dynamics as a Localizing Factor for Atherosclerosis”, pp. 60–70, G. Schettler, ed., Springer-Verlag, Heidelberg (1983).CrossRefGoogle Scholar
  14. 14.
    C.F. Dewey, Jr, Dynamics of arterial flow, Adv Exp Med Biol 115:55–103 (1979).Google Scholar
  15. 15.
    M.H. Friedman, C.B. Bargeron, C.M. Hutchins, F.F. Mark, and O.J. Deters, Hemodynamic measurements in human arterial casts and their correlation with histology and luminal area, J Biomech Eng 102:247–251 (1980).PubMedCrossRefGoogle Scholar
  16. 16.
    T. Karino and H.L. Goldsmith, Disturbed flow in models of branching vessels, Trans Am Soc Artif Intern Organs 26:500–505 (1980).PubMedGoogle Scholar
  17. 17.
    D.N. Ku and D.P. Giddens, Laser Doppler anemometer measurement of pulsatile flow in a model carotid bifurcation, J Biomech 20:407–421 (1987).PubMedCrossRefGoogle Scholar
  18. 18.
    R.J. Lutz, J.N. Cannon, K.B. Bischoff, R.L. Dedrick, R.K. Stiles, and D.L. Fry, Wall shear stress distribution in a model canine artery during steady flow, Circ Res 41:391–399 (1977).PubMedGoogle Scholar
  19. 19.
    S. Glagov, E. Weisenberg, C.K. Zarins, M.P. Stankunavicius, and B.A. Kolettis, Compensatory enlargement of human atherosclerotic coronary arteries, New Engl J Med 316:1371–1375 (1987).PubMedCrossRefGoogle Scholar
  20. 20.
    S. Glagov, Hemodynamic risk factors: mechanical stress, mural architecture, medial nutrition and the vulnerability of arteries to atherosclerosis, in: “The Pathogenesis of Atherosclerosis”, pp. 164–199, R.W. Wissler and J.C Geer, eds., Williams and Watkins, Baltimore, (1972).Google Scholar
  21. 21.
    C.K. Zarins, D.P. Giddens, B.K. Bharadvaj, V.S. Sottiurai, R.F. Mabon, and S. Glagov, Carotid bifurcation atherosclerosis. Quantitative correlation of plaque localization with flow velocity profiles and wall shear stress, Circ Res 53:502–514 (1983).PubMedGoogle Scholar
  22. 22.
    D.N. Ku, D.P. Giddnes, C.K. Zarins, and S. Glagov, Pulsatile flow and atherosclerosis in the human carotid bifurcation. Positive correlation between plaque location and low and oscillating shear stress, Arteriosclerosis 5:293–301 (1985).PubMedCrossRefGoogle Scholar
  23. 23.
    D.N. Ku and D. Liepsch, The effects of non-newtonian viscoelasticity and wall elasticity on flow at a 90 bifurcation, Biorheology 23:359–370 (1986).PubMedGoogle Scholar
  24. 24.
    J.T. Flahery, J.E. Pierce, V.J. Ferrans, D.J. Patel, W.K. Tucker, and D.L. Fry, Endothelial nuclear patterns in the canine arterial tree with particular reference to hemodynamic events, Circ Res 30:23–32 (1972).Google Scholar
  25. 25.
    C.F. Dewey, S.R. Bussolari, M.A. Gimbrone, and P.F. Davies, The dynamic response of vascular endothelial cells to fluid shear stress, J Biomech Engin 103:177–185 (1981).CrossRefGoogle Scholar
  26. 26.
    A. Remuzzi, C.F. Dewey, P.F. Davies, and M.A. Gimbrone, Orientation of endothelial cells in shear fields in vitro, Biorheology 21:617–630 (1984).PubMedGoogle Scholar
  27. 27.
    M. Sato, M.J. Levesque, and R.M. Nerem, Micropipette aspiration of cultured bovine aortic endothelial cells exposed to shear stress, Arteriosclerosis 7:276–286 (1987).PubMedCrossRefGoogle Scholar
  28. 28.
    P.F. Davies, C.F. Dewey, S.R. Bussolari, E.J. Gordon, and M.A. Gimbrone, Influence of hemodynamic forces on vascular endothelial function, J Clin Invest 73:1121–1129 (1984).PubMedCrossRefGoogle Scholar
  29. 29.
    E.A. Sprague, V.L. Steinbach, R.M. Nerem, and C.J. Schwartz, Influence of a laminar steady-state fluid-imposed wall shear stress on the binding, internalization and degradation of low density lipoproteins by cultured arterial endothelium, Circulation 76:648–656 (1987).PubMedCrossRefGoogle Scholar
  30. 30.
    S.M. Schwartz, and Benditt, E.P. Benditt, Clustering of replicating cells in aortic endothelium, Proc Natl Acad Sci USA 73:651–653 (1976).PubMedCrossRefGoogle Scholar
  31. 31.
    S.M. Schwartz, Selection and characterization of bovine aortic endothelial cells, In Vitro 14:966 (1978).PubMedCrossRefGoogle Scholar
  32. 32.
    B.A. Caplan, and C.J. Schwartz, Increased endothelial cell turnover in areas of in vivo Evans Blue uptake in the pig aorta, Atherosclerosis 17:401 (1973).PubMedCrossRefGoogle Scholar
  33. 33.
    H.P. Sdougos, S.R. Bussolari, and C.F. Dewey, Secondary flow and turbulence in a cone-and-plate device, J Fluid Mech 138:379–404 (1984).CrossRefGoogle Scholar
  34. 34.
    S.L. Diamond, S.G. Eskin, and L.V. McIntire, Fluid flow stimulates tissue plasminogen activator secretion by cultured human endothelial cells, Science 243:1483–1485 (1989).PubMedCrossRefGoogle Scholar
  35. 35.
    M. Yoshizumi, M. Murihara, T. Sugiyama, F. Takaku, M. Yanagisawa, T. Masaki, and Y. Yazaki, Hemodynamic shear stress stimulates endothelin production by cultured endothelial cells, Biochem Biophys Res Comm 161:859–864 (1989).PubMedCrossRefGoogle Scholar
  36. 36.
    A.J. Hudspeth, How the ear’s works work, Nature 341:397–404 (1989).PubMedCrossRefGoogle Scholar
  37. 37.
    S.P. Olesen, D.E. Clapham, and P.F. Davies, Haemodynamic shear stress activates a K+ current in vascular endothelial cells, Nature 331:168–170 (1988).PubMedCrossRefGoogle Scholar
  38. 38.
    J.B. Lansman, T.J. Hallam, and T.J. Rink, Single stretch-activated ion channels in vascular endothelial cells as mechanotransducers, Nature 325:811–813 (1987).PubMedCrossRefGoogle Scholar
  39. 39.
    P.F. Davies, How do vascular endothelial cells respond to flow?,News in Physiol Sci (NIPS) 4:22–26 (1989).Google Scholar
  40. 40.
    P.F. Davies, S.P. Olesen, D.E. Clapham, E.E. Morrel, and F.J.Schoen, Endothelial Communication, Hypertension 11:563–572 (1988).PubMedGoogle Scholar
  41. 41.
    P.M. VanHoutte, G.M. Rubanyi, V.M. Miller, and D.S. Houston, Endothelial relaxing factors, Ann Rev Physiol 48:307–320 (1986).CrossRefGoogle Scholar
  42. 42.
    R. Busse, H. Fichtner, A. Luckhoff, and M. Kohlhardt, Hyperpolarization and increased free calcium in Ach stimulated endothelial cells, Am J Physiol 255:H965–H969.Google Scholar
  43. 43.
    E.F. Grabowski, E.A. Jaffe, and B.B. Weksler, Protascyclin production by cultured endothelial cell monolayers exposed to step increases in shear stress, J Lab Clin Med 105:36–43 (1985).PubMedGoogle Scholar
  44. 44.
    J.A. Frangos, S.G. Eskin, L.V. McIntire, and C.L. Ives, Flow Effects on Prostacyclin Production by Cultured Human Endothelial Cells, Science 227:1477–1479 (1985).PubMedCrossRefGoogle Scholar
  45. 45.
    R.O. Dull, and P.F. Davies, Differential endothelial cytosolic calcium responses to hemodynamic shear stress in vitro, Circulation Suppl 2:481 (1989).Google Scholar
  46. 46.
    M.J. Berridge, and R.F. Irvine, Inositol Phosphates and cell signalling, Nature 341:197–205.Google Scholar
  47. 47.
    B.L. Langille, M.A. Reidy, and R.L. Kline, Injury and repair of endothelium at sites of flow disturbances near abdominal aortic coarctations in rabbits, Arteriosclerosis 6:146–154 (1986).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Peter F. Davies
    • 1
  • Randal O. Dull
    • 1
  1. 1.Department of Pathology, Pritzker School of MedicineUniversity of ChicagoUSA

Personalised recommendations