Injury at the Vascular Surface

  • S. M. Schwartz
  • M. A. Reidy
  • G. K. Hansson


The last ten years have seen an exponential growth in interest in, the role of the endothelium in atherosclerosis and in the idea that suggests that the cell affected by shear, the endothelial cell, may play a critical role in lesion formation. This interest has come from two quite different sources. First, there is the apparent coincidence of areas of high shear with areas with a propensity to develop atherosclerosis. Second, there is the biochemical evidence that the endothelial cell is intensively active in a number of metabolic functions capable of modulating lesion formation. All of this has tended to blur our lack of a definition for endothelial injury. For example, Ross’ and Harker’s (1976) discovery of the platelet-derived growth factor (PDGF) led to a major emphasis on denuding injuries as a site where platelets could interact with the vessel wall and stimulate smooth muscle proliferation. Actual studies of denuding injuries, however, have been very limited except over advanced lesions or in response to the balloon catheter. Studies of hypertensive or hyperlipemic animals have not shown denudations unless overt atherosclerotic lesions were already present (Schwartz et al. 1980; Hansson and Bondjers 1980).


Endothelial Injury Bovine Aortic Endothelial Cell Rabbit Aorta Aortic Endothelium Endothelial Cell Death 
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  1. Assmussen I, Kjeldsen K (1975) Intimai ultrastructure of umbilical arteries. Observations on arteries from newborn children of smoking and nonsmoking mothers. Circ Res 36: 579–589Google Scholar
  2. Bell FP, Gallus AS, Schwartz CJ (1974) Focal and regional patterns of uptake and the transmural distribution of 131I-fibrinogen in the pig aorta in vivo. Exp Mol Pathol 20: 281–292PubMedCrossRefGoogle Scholar
  3. Björkerud S, Bondjers G (1972) Endothelial integrity and viability in the aorta of the normal rabbit and rat as evaluated with dye exclusion tests and interference contrast microscopy. Atherosclerosis 15: 285–300PubMedCrossRefGoogle Scholar
  4. Bylock A, Björkerud S, Brattsand R, Hansson GK, Hansson H-A, Bondjers G (1977) Endothelial structure in rabbits with moderate hypercholesterolemia. Acta Pathol Microbiol Scand [A] 85: 671–682Google Scholar
  5. Chandler AB, Pope JJ (1975) Arterial thrombosis and atherogenesis, a survey of the frequency of incorporation of thrombi into atherosclerotic plaques. In: Hautvast JGAJ, Hermus RJJ, Van Der Haar F (eds) Blood and arterial wall in atherogenesis and arterial thrombosis. ET Brill, Leiden, p 110Google Scholar
  6. Chien KR, Abrams J, Pfau RG, Farber JL (1977) Prevention by chlorpromazine of ischemic liver cell death. Am J Pathol 88: 539–558PubMedGoogle Scholar
  7. Clark JM, Glagov S (1976) Luminal surface of distended arteries by scanning electron microscopy: elimination of contiguational and technical artefacts. Brit J Exp Pathol 57: 129–135Google Scholar
  8. Davies PF, Bowyer DE (1975) Scanning electron microscopy: arterial endothelial integrity after fixation at physiological pressure. Atherosclerosis 21: 463–470PubMedCrossRefGoogle Scholar
  9. deDuve C (1964) Lysosomes and cell injury. In: Thomas L, Uhr JW, Grant L (eds) Injury, inflammation and immunity. Williams and Wilkins, Baltimore, p 283Google Scholar
  10. Ericsson JLE, Brunk UT (1977) Alterations in lysosomal membranes as related to disease processes. In: Trump BF, Arstila AU (eds) Pathobiology of cell membrane, vol I. Academic Press, New York, p 217Google Scholar
  11. Farber JL, Chien KR, Mittnacht S (1981) The pathogenesis of irreversible cell injury in ischemia. Am J Pathol 102: 271–281PubMedGoogle Scholar
  12. Florentin RA, Nam SC, Lee KT, Thomas WA (1969) Increased 3H-thymidine incorporation into endothelial cells of swine fed cholesterol for three days. Exp Mol Pathol 10: 250–255PubMedCrossRefGoogle Scholar
  13. Fowler S, Shio H, Haley NJ (1979) Characterization of lipid-laden aortic cells from cholesterol-fed rabbits. IV. Investigation of macrophage-like properties of aortic cell populations. Lab Invest 41: 372–378PubMedGoogle Scholar
  14. French JE (1966) Atherosclerosis in relation to the structure and function of arterial intima, with special reference to the endothelium. Int Rev Exp Pathol 5: 253–353PubMedGoogle Scholar
  15. Fry DL (1968) Acute vascular endothelial changes associated with increased blood velocity gradients. Circ Res 22: 165–197PubMedGoogle Scholar
  16. Gaynor E (1971) Increased mitotic activity in rabbit endothelium after endotoxin. An autoradiographic study. Lab Invest 24: 318–320PubMedGoogle Scholar
  17. Gerrity RG, Naito HK, Richardson M, Schwartz CJ (1979) Dietary induced athero-genesis in swine: morphology of the intima in pre-lesion stages. Am J Pathol 95: 775–786PubMedGoogle Scholar
  18. Goldberg ID, Stemerman MB, Handin RI (1980) Vascular permeation of platelet factor IV after endothelial injury. Science 209: 610–612CrossRefGoogle Scholar
  19. Hansson GK, Bondjers G (1980) Endothelial proliferation and atherogenesis in rabbits with moderate hypercholesterolemia. Artery 7: 316–329PubMedGoogle Scholar
  20. Hansson GK, Bondjers G, Nilsson L-Å (1979) Plasma protein accumulation in injured endothelial cells. Immunofluorescent localization of IgG and fibrinogen in the rabbit aortic endothelium. Exp Mol Pathol 30: 12–26PubMedCrossRefGoogle Scholar
  21. Hansson GK, Bondjers G, Bylock A, Hjalmarsson L (1980) Ultrastructural studies on the localization of IgG in the aortic endothelium and subendothelial intima of atherosclerotic and non-atherosclerotic rabbits. Exp Mol Pathol 33: 302–315PubMedCrossRefGoogle Scholar
  22. Hansson GK, Björnheden T, Bylock A, Bondjers G (1981) Fc-dependent binding of monocytes to areas with endothelial injury in the rabbit aorta. Exp Mol Pathol 34: 264–280PubMedCrossRefGoogle Scholar
  23. Hansson GK, Schwartz SM (1982a) Evidence for cell death in the aortic endothelium. Fed Proc (in press)Google Scholar
  24. Hansson GK, Bondjers G, Schwartz SM (1982) Focal cell death in the arterial endothelium (submitted)Google Scholar
  25. Hansson GK, Schwartz SM (1982b) Endothelial dysfunction without cell loss. In: Cryer A (ed) Biochemical interactions at the endothelium. Elsevier/North Holland Biomedical Press, London (in press)Google Scholar
  26. Hawkins HK, Ericsson JLE, Biberfeld P, Trump BF (1972) Lysosome and phagosome stability in lethal cell injury. Am J Pathol 68: 255–288PubMedGoogle Scholar
  27. Hugod C, Hawkins LH, Kjeldsen K, Thomsen HK, Astrup P (1978) Effect of carbon monoxide exposure on aortic and coronary intimai morphology in the rabbit — a re-evaluation. Atherosclerosis 30: 333–342PubMedCrossRefGoogle Scholar
  28. Jennings RB, Ganote CE, Reimer K (1975) Ischemic tissue injury. Am J Pathol 81: 179–198PubMedGoogle Scholar
  29. Kane AB, Stanton RP, Rayond EG, Dobson ME, Knafelc ME, Farber JL (1980) Dissociation of intracellular lysosomal rupture from the cell death due to silica. J Cell Biol 87: 643–651PubMedCrossRefGoogle Scholar
  30. Kunz J, Schreiter B, Schubert B, Voss K, Krieg K (1978) Experimentelle Untersuchungen über die Regeneration der Aortenendothelzellen. Automatische und visuelle Auswertung von Autoradiogrammen. Acta Histochem 61: 53–63PubMedGoogle Scholar
  31. Laiho KU, Trump BF (1977) The relationship between cell viability and changes in mitochondrial ultrastructure, cellular ATP, ion and water content following injury of Ehrlich ascites tumor cells. Virchows Arch Cell Pathol 15: 264–277Google Scholar
  32. Linder E (1981) Binding of Clq and complement activation by vascular endothelium. J Immunol 126: 648–658PubMedGoogle Scholar
  33. Mittnacht S Jr, Sherman SC, Farber JL (1979) Reversal of ischemic motichondrial dysfunction. J Biol Chem 254: 9871–9878PubMedGoogle Scholar
  34. Mustard JF, Packham MA, Kinlough-Rathbone RL (1981) Platelets, atherosclerosis and clinical complications. In: Moore S (ed) Vascular injury and atherosclerosis. Dekker, New York, p 79Google Scholar
  35. Reidy MA, Bowyer DE (1977) Scanning electron microscopy. Morphology of aortic endothelium following injury by endotoxin and during subsequent repair. Atherosclerosis 26: 319–328PubMedCrossRefGoogle Scholar
  36. Reidy MA, Schwartz SM (1980) Developments in the study of endothelial cells by scanning electron microscopy. Artery 8: 236–243PubMedGoogle Scholar
  37. Reidy MA, Schwartz SM (1981) Endothelial regeneration. III. Time course of intimai changes after small defined injury of rat aortic endothelium. Lab Invest 44: 301–308PubMedGoogle Scholar
  38. Reidy MA, Schwartz SM (1982) Endothelial regeneration. IV. The effect of endotoxin on arterial endothelium. Lab Invest (in press)Google Scholar
  39. Ross R, Harker L (1976) Hyperlipidemia and atherosclerosis. Chronic hyperlipidemia initiates and maintains lesions by endothelial cell desquamation and lipid accumulation. Science 193: 1094–1100PubMedCrossRefGoogle Scholar
  40. Ross R, Schwartz SM (1982) Endothelial interactions. In: Fisher AB, Fishman AP (eds) Handbook of physiology, vol IV. The Americal Physiological Society, Bethesda (in press)Google Scholar
  41. Schwartz SM (1978) Selection and characterization of bovine aortic endothelial cells. In Vitro 14: 966–980PubMedCrossRefGoogle Scholar
  42. Schwartz SM, Benditt EP (1973) Cell replication in the aortic endothelium: a new method for study of the problem. Lab Invest 28: 699–707PubMedGoogle Scholar
  43. Schwartz SM, Benditt EP (1976) Clustering of replicating cells in aortic endothelium. Proc Nat Acad Sci 73: 651–653PubMedCrossRefGoogle Scholar
  44. Schwartz SM, Benditt EP (1977) Aortic endothelial cell replication. II. Effects of age and hypertension in the rat. Circ Res 41: 148–255Google Scholar
  45. Schwartz SM, Gajdusek CM, Reidy MA, Seiden SC, III, Haudenschild CC (1980) Maintenance of integrity in aortic endothelium. Fed Proc 39: 2618–2625PubMedGoogle Scholar
  46. Schwartz SM, Stemerman MB, Benditt EP (1975) The aortic intima. II. Repair of the aortic lining after mechanical denudation. Am J Pathol 81: 15–52PubMedGoogle Scholar
  47. Spangoli LG, Pietra GG, Villuschi S, Johns LW (1981) Morphometric analysis of gap junctions in regenerating arterial endothelium. Lab Invest 46: 139–148Google Scholar
  48. Stemerman MB (1981) Effects of moderate hypercholesterolemia on rabbit endothelium. Arteriosclerosis 1: 25–32PubMedCrossRefGoogle Scholar
  49. Svendsen E (1979) Focal endothelial injury in rabbit aorta. Aggravation of injury by two days of cholesterol feeding. Acta Pathol Microbiol Scand [A] 87: 123–130Google Scholar
  50. Thomas WA, Reiner JM, Florentin RA, Scott RF, Lee KT, Janakidevi K (1981) Population dynamics of arterial cells in atherogenesis. In: Moore S (ed) Vascular injury and atherosclerosis. Dekker, New York, p 111Google Scholar
  51. Trump BF, Arstila AU (1975) Cell membrane and disease processes. In: Trump BF, Arstila AU (eds) Pathobiology of cell membranes, vol I. Academic Press, New York, p 1Google Scholar
  52. Velican C, Velican D (1979) Study on the onset of atherosclerotic lesions in human coronary arteries. Rev Roum Med-Med Int 17: 131–149Google Scholar
  53. Weber G, Fabbrini P, Resi L (1974) Scanning and transmission electron microscopy observations on the surface lining of aortic intimai plaques in rabbits on a hypercholesterolic diet. Virchows Arch Pathol Anat 364: 325–331PubMedGoogle Scholar
  54. Wright HP (1972) Mitosis patterns in aortic endothelium. Atherosclerosis 15: 93–100PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1983

Authors and Affiliations

  • S. M. Schwartz
  • M. A. Reidy
  • G. K. Hansson

There are no affiliations available

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