The Role of Arterial Endothelial Cell Mitosis in Macromolecular Permeability

  • Shu Chien
  • Shing-Jong Lin
  • Sheldon Weinbaum
  • Mary M. L. Lee
  • Kung-Ming Jan
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 242)


Atherosclerosis is characterized by focal areas of lipid accumulation and intimal smooth muscle cell proliferation. Atherosclerotic lesions tend to develop in preferential areas in the aortic tree,1 where transendothelial macromolecular permeability is high as indicated by an enhanced uptake of the protein-binding azo dye Evans Blue in vivo.2–4 These so-called blue areas have been shown to be associated with an increased rate of endothelial cell turnover3,5 and an enhanced permeability to low density lipoproteins (LDL).6 The subendothelial accumulation of unesterified cholesterol has been hypothesized to be an initial event in atherogenesis.7 The mechanism by which macromolecules such as LDL or albumin enter the arterial wall, however, is still not completely understood.


Evans Blue Subendothelial Space Aortic Endothelium Open Junction Macromolecular Permeability 
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.
    S Glagov, Hemodyamic risk factors: Mechanical stress, mural architecture, medial nutrition and the vulnerability of arteries to atherosclerosis, In: “The pathogenesis of athrosclerosis,” R.W. Wissler and J.C. Geer, ed., Baltimore, Wilhams and Wilkins Press, (1972).Google Scholar
  2. 2.
    M.A. Packham, H.C. Rowsell, L. Jorgensen and J.F. Mustard, Localized protein accumulation in the wall of the aorta, Exptl Molec Pathol 7:214–232 (1967).CrossRefGoogle Scholar
  3. 3.
    B.A. Caplan and C.J. Schwartz, Increased endothelial cell turnover in areas of in vivo Evans Blue uptake in the pig aorta. Atherosclerosis 17:401–417 (1973).PubMedCrossRefGoogle Scholar
  4. 4.
    R.G. Gerrity, M. Richardson, J.B. Somer, P.P. Bell and C.J. Schwartz, Endothelial cell morphology in area of in vivo Evans Blue uptake in the aorta of young pigs. II. Ultrastructure of the intima in area of differing permeability to proteins. Am J Pathol 89:313–334 (1977).PubMedGoogle Scholar
  5. 5.
    S.M. Schwartz, E.P. Benditt, Clustering of replicating cells in aortic endothelium, Proc Natl Acad Sci USA 73:651–653 (1976).PubMedCrossRefGoogle Scholar
  6. 6.
    C.J. Schwartz, E.A. Sprague, S.R. Fowler and J.L. Kelley, Cellular participation in atherogenesis: selected facets of endothelium, smooth muscle and the periheral blood monocyte. In “Fluid Dynamics as a Localizing Factor for Atherosclerosis,” G. Schettler ed.. Springer-Verlag Press, Berlin (1983)Google Scholar
  7. 7.
    H.S. Kruth, Subendothelial accumulation of unesterified cholesterol. An early event in atherosclerotic lesion development. Atherosclerosis 57:337–341 (1985).PubMedCrossRefGoogle Scholar
  8. 8.
    D. Steinberg, Lipoproteins and atherosclerosis. A look back and a look ahead, Arteriosclerosis 3:283–301 (1983).PubMedCrossRefGoogle Scholar
  9. 9.
    M.A. Reidy and S.M. Schwartz, Developments in the study of endothelial cells by scanning electron microscopy. Artery 8:236–243 (1980).PubMedGoogle Scholar
  10. 10.
    C.K. Zarins, K.E. Taylor, R.A. Bomberger and S. Glagov, Endothelial integrity at aortic ostial flow dividers, Scan Electron Microsc 3:249–254 (1980).PubMedGoogle Scholar
  11. 11.
    R.M. Nerem, M.J. Levesque and J.F. Cornhill, Vascular endothelial morphology as an indicator of the pattern of blood flow, ASME J. Biomech Eng 103:172–176 (1981).CrossRefGoogle Scholar
  12. 12.
    W.E. Stehbens, Endothelial cell mitosis and permeability,Q J Exp Physiol 50:90–92 (1965).Google Scholar
  13. 13.
    S. Weinbaum, G. Tzeghai, P. Ganatos, R. Pfeffer and S. Chien, Effect of cell turnover and leaky junctions on arterial macromolecular transport. Am J Physiol 248:H945-H960 (1985).PubMedGoogle Scholar
  14. 14.
    S. Weinbaum, G.B. Wen, P. Ganatos, R. Pfeffer, M. Lee and S. Chien, On the transient diffusion of macromolecules through leaky junctions and their subendothelial spread; Part I. Short time model for cleft exit region, J Theor Biol, in press (1988).Google Scholar
  15. 15.
    G.B. Wen, S. Weinbaum, P. Ganatos, R. Pfeffer and S. Chien, On the transient diffusion of macromolecules through leaky junctions and their subendothelial spread; Part II. Long time model for interaction between leakage sites, 7. Theor Biol, in press (1988).Google Scholar
  16. 16.
    S.J. Lin, K.M. Jan S. Weinbaum and S. Chien, Enhanced macromolecular permeability of aortic endothelial cells in association with mitosis. Atherosclerosis, in press (1988).Google Scholar
  17. 17.
    T. Zand, J.M. Underwood, J.J. Nunnari, G. Majno and I. Joris, Endothelium and “silver lines”. An electron microscopic study, Virchows Arch [Pathol Ana] 395:133–144 (1982).CrossRefGoogle Scholar
  18. 18.
    M. Bundgaard, The three dimensional organisation of tight junctions in a capillary with continuous endothelium revealed by serial section electron microscopy, J Ultrastruct Res 88:1–17 (1984).PubMedCrossRefGoogle Scholar
  19. 19.
    S.H. Song and M.R. Roach, Qauntitative changes in the size of fenestrations of the elastic laminae of sheep thoracic aorta studied with SEM, Blood Vessels 20:145–153 (1983).PubMedGoogle Scholar
  20. 20.
    E.B. Smith and E.M. Staples, Plasma protein concentrations in interstitial fluid from human aortas, Proc Roy Soc London B217:59–75 (1982).Google Scholar
  21. 21.
    D. Fry, Mass transport, atherogenesis and risk, Arteriosclerosis 7:88–100 (1987).PubMedCrossRefGoogle Scholar
  22. 22.
    M.J. Karnovasky, The ultrastructural basis of capillary permeability studies with peroxidase as atracer, J Cell Biol 35:213–236 (1967).CrossRefGoogle Scholar
  23. 23.
    M.B. Stemerman, E.M. Morrel, K.R. Burke, C.K. Colton, K.A. Smith and R.S. Lees, Local variation in arterial wall permeability to low density lipoprotein in normal rabbit aorta. Arteriosclerosis, 6:64–69 (1986).PubMedCrossRefGoogle Scholar
  24. 24.
    S.M. Schwartz and E.P. Benditt, Cell replication in the aortic endothelium: A new method for study of the problem. Lab Invest 28:699–707 (1973).PubMedGoogle Scholar
  25. 25.
    G.E. White, M.A. Gimbrone and K. Fujiwara, Factors influencing the expression of stress fibers in vascular endothelial cells in site, J Cell Biol 97:14–24 (1983).Google Scholar
  26. 26.
    I. Huttner, C. Walker and G. Gabbiani, Aortic endothelial cell during regeneration. Remodeling of cell junctions, stress fibers, and stress fiber-membrane attachment domains. Lab Invest 53:287–302 (1985).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Shu Chien
    • 1
    • 2
  • Shing-Jong Lin
    • 1
    • 2
  • Sheldon Weinbaum
    • 3
  • Mary M. L. Lee
    • 2
  • Kung-Ming Jan
    • 1
    • 2
  1. 1.Institute of Biomedical SciencesAcademia SinicaTaipei, 11529Taiwan, ROC
  2. 2.Department of Physiology and Cellular Biophysics College of Physicians and SurgeonsColumbia UniversityNew YorkUSA
  3. 3.Department of Mechanical EngineeringCity College of the City University of New YorkNew YorkUSA

Personalised recommendations