Advertisement

Mechanics of the Endothelium in Blood Flow

  • Y. C. Fung
  • S. Q. Liu

Abstract

The endothelium is a single layer of confluent endothelial cells covering the entire inner wall of the heart and blood vessels. It is a mono layer (i. e. no cell stays on the back of another) resting on a collagenous basal lamina, with a thickness of from 2 to 5 μm, the higher spots reveling the cell nuclei. The endothelium separates blood from tissue. It’s importance to the circulation is somewhat analogous to the skin to a man, the roof to a house, the semipermeable membrane of a reverse osmosis water desalination plant, i. e., it separates; filtrates, and controls the mass transport between the tissue and the blood. It carries enzymes, and manufactures many of them, which control the clotting of blood, dissolution of clots, adhesion of leukocytes or cancer cells, passage of LDL, growth of new blood vessels, as well as inhibition of growth. Molecular biology of the endothelial cells responding to the shear stress of the flowing blood is advancing very rapidly. Paper by P.F. Davies (10, 11, 12), D.F. Dewey, Jr. (13, 55) J.A. Frangos (15), M.A. Gimbrone, Jr. (10, 55, 56). Kuo et. al. (38), Levesque et. al. (40), L.V. McIntire (18, 50), Nerem et. al. (49), Resnick et. al. (56), Sato et. al. (62, 63). Smiesko and Johnson (71), and others have opened up a new vista to biology. It has been found that the locally produced growth factors include the growth promotors such as the platelet-derived growth factor (PDGF), (30, 44, 59), and the vascular endothelium-derived growth factor (VEFG), (26, 28, 47, 48, 60), and the growth inhibitors such as the endothelium-derived relaxation factor (EDRF) nitric oxide (5, 37, 46). Evidences are mounting that hypertension induces up-regulation of growth promoting substances and their receptors (Sarzani et. al. (59), and down-regulation of growth inhibitory factors EDRF and prostacyclin (Luscher et. al. (43), Panza et. al. (52)). It is established that gene expressions are functions of stress and strain, (Resnick et. al. (56), Shyy et. al. (66), and cell integrity, growth, and differentiation are influenced by stress and strain (Ingber et. al. (31, 32))

Keywords

Endothelial Cell Shear Stress Tensile Stress Side Wall Cell Content 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Barbee, K. A., Davies, R.F., and Lal, R.: Shear stress-induced reorganization of the surface topography of living endothelial cells imaged by atomic force microscopy. Cir. Res. 74: 163–171, 1994.CrossRefGoogle Scholar
  2. 2.
    Barbee, K.A., Macarak, E.J., Thibault, L.E.: Strain measurements in cultured vascular smooth muscle cells subjected to mechanical deformation. Ann. Biomed. Eng. 22: 14–22, 1994.PubMedCrossRefGoogle Scholar
  3. 3.
    Barer, R. and Joseph, S.: Refractometry of living cells Part 1, Basic principles Part 2, The immersion medium. Q. J. Micros. Sci. 95: 399–423, 1954 and 96: 1-27, 1955.Google Scholar
  4. 4.
    Caro, C.G., Fitz-Gerald, J.M., and Schroter, R.C.: Atheroma and arterial wall shear-observation, correlation, and proposal of a shear-dependent mass-transfer mechanism for atherogenesis. Proceed, of Roy. Soc., London, [Biol.] 177: 109–159, 1971.CrossRefGoogle Scholar
  5. 5.
    Chen R.Y.Z. Chang Ch.H. and P.H. Guth. gastric arteriolar and venular responses to nitrogeneous and nonnitrogenous vasodilating agents in the rats. Int. J. Microcirc. 14: 197–203, 1994.CrossRefGoogle Scholar
  6. 6.
    Chuong, C.J., and Fung, Y.C.: “On residual stress in arteries,” J. Biomech. Eng. 108: 189–192, 1986.PubMedCrossRefGoogle Scholar
  7. 7.
    Curry, F-R.E.: Mechanics and thermodynamics of transcapillary exchange. In Handbook of Physiology, — Cardiovascular System IV, Part I, pp. 309–374, American Physiological Society, Bethesda, MD.Google Scholar
  8. 8.
    Emeis, J.J. and Edgell, C.-J. S.: Fibrinolytic properties of a human endothelial hybrid cell line (Ea. hy 926). Blood. 71: 1669–1675, 1988.PubMedGoogle Scholar
  9. 9.
    Danielson, D.A., and Natarajan, S.: Tension field theory and the stress in stretched skin. J. of Biomech. 8: 135–142, 1975.CrossRefGoogle Scholar
  10. 10.
    Davies, P.F., Dewey, C.F., Bussolari, S.R., Gordon, E.L., and Gimbrone, M.A. Jr.: Influence of hemodynamic forces on vascular endothelial function. In vitro studies of shear stress and pinocytosis in bovine aortic cells. J. Clin. Invest. 73: 1121–1129, 1984.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Davies P.F., and Tripathi S.C.: Mechanical stress mechanisms and the cell An Endothelial paradigm. Circ. Res. 72: 239–245, 1993.PubMedCrossRefGoogle Scholar
  12. 12.
    Davies, P.F., Remuzzi, A., Gordon, E.F., Dewey, C.F., Jr., Gimbrone, M.A., Jr.: Turbulent fluid shear stress induces vascular endothelial cell turnover in vitro. Proc. Natl. Acad. Sci. 83: 2114–2117, 1986.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Dewey, C.F., Bussolari, S.R., Gimbrone, M.A., and Davies, P.F.: The dynamic response of vascular endothelial cells to fluid shear stress. J. Biochemical Engineering 103: 177–185, 1981.Google Scholar
  14. 14.
    Evans, E. and Fung, Y.C.: Improved measurements of the erythrocyte geometry. Microvasc 4: 335–347, 1972.CrossRefGoogle Scholar
  15. 15.
    Frangos, J.A., Eskin S.G., McIntire L.V., Ives C.L.: Flow effects on prostacyclin production by cultured human endothelial cells. Science 227: 1477–1479, 1985.PubMedCrossRefGoogle Scholar
  16. 16.
    Fry, D.L.: Acute vascular endothelial changes associated with increased blood velocity gradients. Circ. Res. 22: 165–197, 1968.PubMedCrossRefGoogle Scholar
  17. 17.
    Fung, Y.C., Zweifach, B.W. and Maglietta, M.: Elastic environment of the capillary bed. Circ. Res. 19: 441–461, 1966.PubMedCrossRefGoogle Scholar
  18. 18.
    Fung, Y.C.: A First Course on Continuum Mechanics. 3rd ed. Prentice Hall, Englewood Cliff, N.J. 1993.Google Scholar
  19. 19.
    Fung, Y.C.: Motion, Flow Stress, and Growth. Springer-Verlag, New York, 1990.Google Scholar
  20. 20.
    Fung, Y.C.: Biomechanics: Mechanical Properties of Living Tissues. Springer-Verlag, New York, 1st ed. 1981. 2nd ed. 1993.CrossRefGoogle Scholar
  21. 21.
    Fung, Y.C., and Liu, S.Q.: Elementary mechanics of the endothelium of blood vessels. J. Biomechanical Engineering, 115: 1–12. 1993.CrossRefGoogle Scholar
  22. 22.
    Fung, Y.C. and Yih, C.S.: Peristaltic transport. J. Appl. Mech. 35, E: 669–675, 1968.CrossRefGoogle Scholar
  23. 23.
    Gau, G.S., Ryder, T.A., and MacKenzie, M.L.: The effect of blood flow on the surface morphology of the human endothelium. J. of Path. 131: 55–60, 1980.CrossRefGoogle Scholar
  24. 24.
    Geister, A.A.T., M.J. Peach, and G.K. Owen: Angiotensin II induces hypertrophy, not hyperplasia, of cultured rat aortic smooth muscle cells. Cir. Res. 62: 747–756, 1988.Google Scholar
  25. 25.
    Giddens, D.P., Zarins, C.K., and Glagov. S.: Response of arteries to near-wall fluid dynamic behavior. App. Mech. Rev. 43: S98–S102, 1990.CrossRefGoogle Scholar
  26. 26.
    Griffin, S.A., W.C.B. Brown, F., MacPherson, J.C., McGrath, V.G. Wilson, N., Korsgard, M.J., Schelling, H., Fischer, and D. Ganten: Angiotensin II and growth: a link to cardiovascular hypertrophy? J. Hypertension 9: 3, 1991.Google Scholar
  27. 27.
    Haldar, K.: Analysis of separation of blood flow in constricted arteries. Arch Mech, Warszawa, 43: 103–109, 1991.Google Scholar
  28. 28.
    Hamet P., Hadrava V, Kruppa U., and Tremblay J.: Transforming growth factor 1 expression and effect in aortic smooth muscle cells from spontaneously hypertensive rats. Hypertension 17: 896–901, 1991.PubMedCrossRefGoogle Scholar
  29. 29.
    Helmlinger, G., Geiger, R.V., Schreck, S., and Nerem, R.M.: Effects of pulsatile flow on cultured vascular endothelial cell morphology. J. of Biomech. Eng. 113: 123–131, 1991.CrossRefGoogle Scholar
  30. 30.
    Hsieh H.J., Li N.Q., Frangos J. A.: Shear-induced platelet-derived growth factor gene expression in human endothelial cells is mediated by protein kinase C. J. Cell Physiol. 150: 52–558, 1992.CrossRefGoogle Scholar
  31. 31.
    Ingber, D.: The riddle of morphogenesis: A question of solution chemistry of molecular cell engineering? Cell 75: 1249–1252, 1993.PubMedCrossRefGoogle Scholar
  32. 32.
    Ingber, D.E. and Folkman, J.: Machanochemical switching between growth and differentiation during fibroblast growth factor-stimulated angiogenesis in vitro: Role of extracellular matrix. J. Cell Biol. 109: 317–330, 1989.PubMedCrossRefGoogle Scholar
  33. 33.
    Johnson, P.C.: Peripheral Circulation, John Wiley, New York, 1978.Google Scholar
  34. 34.
    Kamiya, A., Bukhari, R., and Togawa, T.: Adaptive regulation of wall shear stress optimizing vascular tree function. Bull, of Math. Biol. 46: 127–137, 1984.Google Scholar
  35. 35.
    Kamiya, A. and Togawa, T.: Adaptive regulation of wall shear stress to flow change in the canine carotid artery. American J. Physiol. 239: H14–H21, 1980.Google Scholar
  36. 36.
    Kim, D.W., Langille, B.L., Wong, M.K.K., and Gotlieb. A.L.: Patterns of endothelial microfilament distribution in the rabbit aorta in situ. Circ. Res. 64: 21–31, 1989. See also Arteriosclerosis 9: 439-445, 1989.PubMedCrossRefGoogle Scholar
  37. 37.
    Kishimoto, J., Keverne, E.B., Hardwick, J., and Emson, P.C.: Localization of nitric oxide synthase in the mouse olfactory and vomeronasal system: a histochemical, immunological and in situ hybridization study. Eur. J. Neurosci. 5: 1684–1694, 1993.PubMedCrossRefGoogle Scholar
  38. 38.
    Kuo, L., Davis, M.J., Chilian, W.M.: Endothelium-dependent, flow-induced dilatation of isolated coronary arterioles. American J. Physiol. 259: H1063–H1070, 1990.Google Scholar
  39. 39.
    Lee, J.S. and Fung, Y.C.: Flow in locally constricted tubes at low Reynolds number. J. Appl. Mech. 37: 9–16, 1970.CrossRefGoogle Scholar
  40. 40.
    Levesque, M.J. and Nerem, R.M.: The elingation and orientation of cultured endothelial cells in response to shear stress. J. Biomech. Eng. 107: 341–347, 1985.PubMedCrossRefGoogle Scholar
  41. 41.
    Limas C, Westrum B., Limas C.J.: Comparative effects of hydralazine and Captopril on the cardiovascular changes in spontaneously hypertensive rats. Am. J. Pathol. 117: 360–371, 1984.PubMedCentralPubMedGoogle Scholar
  42. 42.
    Liu, S.Q., Yen, M., and Fung, Y.C.: On measuring the third-dimension of cultured endothelial cells in shear flow. Proc. Nat. Acad. Sci, in press.Google Scholar
  43. 43.
    Luscher T.F., Vanhoutte P.M., Raij L.: Antihypertensive treatment normalizes decreased endothelium dependent relaxations in rats with salt-induced hypertension. Hypertension 9 (suppl. III): III193–III197, 1987.Google Scholar
  44. 44.
    Malek A.M., Gibbons G.H., Dzau V.J., and Izumo S.: Fluid stress differentially modulates expression of genes encoding basic fibroblast growth factor and platelet-derived growth factor B chain in vascular endothelium. J. Clin. Invest. 92: 2013–2021, 1993.PubMedCentralPubMedCrossRefGoogle Scholar
  45. 45.
    Markin, V.S., and Martinac, B.: Mechano sensitive ion channels as reporters of bilayer expansion. A theoretical model. Biophysical J. 60: 1–8, 1991.Google Scholar
  46. 46.
    Miyahara, K. Kawamoto, K., Yui, Y., Toda, K., Yang, L.X., Hattori, R., Aoyama, T., Yamamoto. Y, Doi, Y Ogoshi, S., Hashimoto, K., Kawai, C., Sasayama, S., and Shizuta, Y.: Cloning and structural characterizations of the human endothelial nitric-oxide-synthase gene. Eur. J. Biochem., 223: 719–726, 1994.PubMedCrossRefGoogle Scholar
  47. 47.
    Murphy T.J., Alexander R.W., Griendling K.K., Runge M.S., and Bernstein K.E.: Isolation of a cDNA encoding the vascular type-1 angiotensin II receptor. Nature 351: 233–236, 1991PubMedCrossRefGoogle Scholar
  48. 48.
    Naville, D., Lebrethon, M.C., Hermabon, A.Y., Rouer, E., Benarous, R., Saez, J.M.: Characterization and regulation of the angiotensin II type 1 receptor (binding and mRNA) in human adrenal fasciculata-reticularis cells. FEBS Lett 321: 184–188, 1993.PubMedCrossRefGoogle Scholar
  49. 49.
    Nerem, R.M., and Girard, P.R.: Hemodynamic influence on vascular endothelial biology. Toxic. Path. 18: 572–582, 1990.Google Scholar
  50. 50.
    Nollert, M.U., Diamond, S.L., and McIntire, L.V.: Hydrodynamic shear stress and mass transport modulation of endothelial cell metabolism. Biotech, and Bioeng. 38: 588–602, 1991.CrossRefGoogle Scholar
  51. 51.
    Palade, G.E., and Bruns, R.R.: Structural modulation of plasmalemmal vesicles. J. Cell Biol. 37: 633–649, 1968.PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Panza J.A., Quyyumi A.A., Brush J.E., Epstein S.E.: Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N. Eng. J. Med. 323: 21–22, 1990.Google Scholar
  53. 53.
    Pappenheimer, J.R.: Passage of molecules through capillary walls. Physiol. Rev. 33: 387–423, 1953.PubMedGoogle Scholar
  54. 54.
    Reissner, E.: Tension field theory. Proceed, of 5th Inter. Cong. of Appl. Mech.: pp. 88-92, 1938Google Scholar
  55. 55.
    Remuzzi, A., Dewey, C.F., Davies, P.F., and Gimbrone, M.A.: Orientation of endothelial cells in shear field in vitro. Biorheology 21: 617–630, 1984.PubMedGoogle Scholar
  56. 56.
    Resnick, N., Collins, T., Atkinson, W., Bonthron, D.T., Dewey, D.F., Jr. and Gimbrone, M.A., Jr.: Platelet-derived growth factor B chain promoter contains a cis-acting fluid shear-stress-responsive element. Proc. Nat. Acad. Sci., USA 90: 4591–4595, 1993.CrossRefGoogle Scholar
  57. 57.
    Repin, V.S., Dolgov, V.V., Zaikina O.E., Novikov I.A., Antonov A.S., Nikolaeva N.A., and Smirnov, V.N.: Heterogeneity of endothelium in human aorta. Athero. 50: 35–52, 1984.CrossRefGoogle Scholar
  58. 58.
    Rhodin, J.A.G.: Architecture of the vessel wall. In Handbook of Physiology, Sec. 2, Vascular Smooth Muscle, ed. by D.F. Bohr, A.P. Samlyo, and H.V. Sparks, Jr. American Physiological Society, Bethesda, MD, Chap. 1: 1–32, 1980.Google Scholar
  59. 59.
    Sarzani R., Arnaldi G., Takasaki I., Brecher P., and Chobanian A.V.: Effect of hypertension and again on platelet-derived growth factor and platelet-derived growth factor receptor expression in rat aorta and heart. Hypertension 19 (suppl III): III93–III99, 1991.Google Scholar
  60. 60.
    Sasaki, K., Yamano, Y, Bardhan, S., Iwai, N., Murray, J.J., Hasegawa, M., Matsuda, Y, Inagami, T.: Cloning and expression of a complementary DNA encoding a bovine adrenal angiotensin II type 1 receptor. Nature 351: 230–233. 1991.PubMedCrossRefGoogle Scholar
  61. 61.
    Satcher R.L., Jr., and Dewey, C.F.: The distribution of fluid forces on arterial endothelial cells. In “1991 Advances in Bioengineering,” American Society of Mechanical Engineers, BED Vol. 20: pp. 595–598, 1991.Google Scholar
  62. 62.
    Sato, M. Levesque, M.J. and Nerem, R.M.: Applications of the micropipet technique to the measurement of the mechanical properties of cultured bovine endothelial cells. J. Biomech. Eng. 109: 27–34, 1987.PubMedCrossRefGoogle Scholar
  63. 63.
    Sato, M., Theret, D.P., Wheeler L.T., Ohsima, N., and Neren, R.M.: Application of the micropipette technique to the measurement of the mechanical properties of cultured porcine endothelial cells. J. Biomech. Eng. 109: 27–34, 1987. See also, ibid, 112: 263-268, 1990.PubMedCrossRefGoogle Scholar
  64. 64.
    Schmid-Schönbein, G.W., Sung, K.L.P., Tözeren, H., Skalak, R., and Chien, S.: Passive mechanical properties of human leukocytes. Biophys. J. 36: 243–256, 1981.PubMedCentralPubMedCrossRefGoogle Scholar
  65. 65.
    Sechler, E.E.: “Elasticity in Engineering, “ John Wiley & Sons, 1945.Google Scholar
  66. 66.
    Shyy Y.J., Hsieh H.J., Usami., and Chien S.: Fluid shear stress induces a biphasic response of human monocyte chemotactic protein 1 gene expression in vasuclar endothelium. Proc. Nat. Acad. Sci. USA 91: 4678–4682, 1994.PubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    Simionescu, M., Simionescu, N., and Palade, G.E.: Morphometric data on the endothelium of blood capillaries. J. Cell Biol. 60: 128–152, 1974.PubMedCentralPubMedCrossRefGoogle Scholar
  68. 68.
    Simionescu, M., Simionescu, N., and Palade, G.E.: Segmental differentiations of cell junctions in the vascular endothelium. The microvasculature. J. of Cell Biol. 67: 863–885, 1975. See also, ibid, 68: 705-723, 1976.CrossRefGoogle Scholar
  69. 69.
    Singer, S.J., and Nicolson, G.L.: The fluid mosaic model of the structure of cell membranes. Science 175: 720–731, 1972.PubMedCrossRefGoogle Scholar
  70. 70.
    Skalak, R., Tözeren, A., Zarda, R.P., and Chien, S.: Strain energy function of red blood cell membranes. Biophys. J. 13: 245–264, 1973.PubMedCentralPubMedCrossRefGoogle Scholar
  71. 71.
    Smiesko, V. and Johnson, P.C.: The arterial lumen is controlled by flow-related shear stress. News in Physiological Sciences 8: 34–38, 1993.Google Scholar
  72. 72.
    Wagner, H.: Flat sheet metal girders with a very thin metal web. Z Flugtechn. Motor Luft Schiffahrt 20: 200–314, 1929. Translated into English, NACA TM 604-606.Google Scholar
  73. 73.
    Yamaguchi, T., Hoshiai, K., Okino, H., Sakurai, A., Hanai, S., Masuda, M. and Fujiwara, K.: Presented at 1993 Bioengineering conference, BED Vol 24, ASME, p. 167.Google Scholar
  74. 74.
    Yin, F.C.P., Fung, Y.C.: Peristaltic transport in a circular cylidrical tube. J. Appl. Mech. 36: 579–587, 1969.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Y. C. Fung
    • 1
  • S. Q. Liu
    • 1
  1. 1.University of California, San DiegoLa JollaUSA

Personalised recommendations