Smoking, Catecholamines and their Effects on Endothelial Cell Integrity

  • Göran Bondjer
  • Göran Hansson
  • Gun Olsson
  • Knut Pettersson
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 273)


Atherosclerosis is not uniformly distributed over the arterial surface. The preferential localization of atherosclerotic lesions to areas close to branching points and curvatures suggests that hemodynamic strain may be involved in the initiation of atherogenesis. The actual link between hemodynamic strain and atherogenesis has not been defined, but already Virchow (1856) suggested that injury imposed by the wear and tear of flow might be of significance. When Virchow’s ideas were revitalized in the later sixties and early seventies (Baumgartner and Studer 1966, Björkerud 1969, Bondjers and Björnheden 1970, Stemerman and Ross 1972) the primary emphasis was placed on injury in the form of endothelial denudation. When the subendothelial tissue was exposed by removal of the endothelium, platelets adhere and release growth factors. These growth factors, and in particular PDGF, stimulate underlying smooth muscle cells to proliferate (review with references: Ross 1981) to form an intimai thickening. This concept, the original response-to-injury hypothesis has recently been challenged (reviews with references: Reidy and Schwartz 1984, Reidy 1985). Thus, it has been difficult to demonstrate significant endothelial denudation with exposure of subendothelial tissue in the absence of mechanical injury, and even when such injury is induced smooth muscle proliferation does not necessarily follow.


Tobacco Smoke Cynomolgus Monkey Endothelial Injury Integrity Behavioral Smooth Muscle Proliferation 
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  1. Åblad, B., Björkman, J.-A., Gustafsson, D., Hansson, G., Östlund-Lindqvist A.-M. and Pettersson, K. The role of sympathetic activity in atherogenesis: Effects of beta-blockade, Am. Heart J. 116: 322 (1988).PubMedCrossRefGoogle Scholar
  2. Allen, D. R., Browse, N. L., Rutt, D. L., Butler, L., and Fletcher, C. The effect of cigarette smoke, nicotine and carbon monoxide on the permeability of the arterial wall. J. Vasc. Surg. 7: 139 (1988).PubMedGoogle Scholar
  3. Asmussen, I., and Kjeldsen, K. Intimal ultrastructure of human umbilical arteries. Circ. Res. 36: 579 (1975).PubMedGoogle Scholar
  4. Baumgartner, H. R., and Studer, A. Folgen des Gefässkathererismus am normo- under hypercholesterinaemischen Kaninchen. Pathol. Microbiol. 29: 393 (1966).Google Scholar
  5. Björkerud, S. Atherosclerosis initiated by mechanical trauma in normolipidemic rabbits. J. Atheroscler. Res. 9: 209 (1969).PubMedCrossRefGoogle Scholar
  6. Björkerud, S., and Bondjers, G. 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 (1972).PubMedCrossRefGoogle Scholar
  7. Bondjers, G., and Björnheden, T. Experimental atherosclerosis induced by mechanical trauma in rats. Atherosclerosis 12: 301 (1970).PubMedCrossRefGoogle Scholar
  8. Bondjers, G., Bylock, A., Hansson, G., Jonasson, L., and Olofsson, S.-O. The effects of cigarette smoking on aortic endothelial integrity in guinea pigs, as evaluated by scanning electron microscopy, dye exclusion tests, immunohistochemical techniques and mitotic activity. In preparation (1989).Google Scholar
  9. Bylock, A., Bondjers, G., Jansson, I., and Hansson, H.-A. Surface ultrastructure of human arteries with special reference to the effects of smoking. Acta Path. Microbiol. Scand. Sect. A: 87: 201 (1978).Google Scholar
  10. Davis, J. W., Shelton, L., Eigenberg, D. A., and Hignite, C.E. Lack of effect of aspirin on cigarette smoke-induced increase in circulating endothelial cells. Haemostrasis 7: 66 (1987).Google Scholar
  11. Davis, J. W., Shelton, L., Eigenberg D. A., Hignite, C. E., and Watanabe, I. S. Effects of tobacco and non-tobacco cigarette smoking on endothelium and platelets. Clin. Pharmacol. Ther. 37: 529 (1985).PubMedCrossRefGoogle Scholar
  12. Dimsdale, J. E. A perspective on type A behaviour and coronary disease. N. Engl. J. Med. 318: 110 (1988).PubMedCrossRefGoogle Scholar
  13. Epstein, L. H., and Jennings, J. R. Smoking, stress, cardiovascular reactivity and coronary heart disease. In Handbook of Stress, Reactivity and Cardiovascular Disease. Edited by Matthews, K. A., Weiss, S. M., Detre, T., Dembroski T. M. Falkner, B., Manuck, S. B., Williams, R. B. Wiley and Sons, New York, p. 291 (1986).Google Scholar
  14. Hansson, G. K., and Schwartz, S. M. Evidence for cell death in the vascular endothelium in vivo and in vitro. Amer. J. Path. 112: 278 (1983).PubMedGoogle Scholar
  15. Hansson, G. K., Bondjers, G., and Nilsson, L. Å. Plasma protein accumulation in injured endothelial cells. Exp. Mol. Pathol. 30: 12 (1983).CrossRefGoogle Scholar
  16. Hansson, G. K., Bondjers, G., G., Bylock, A., and Hjalmarsson, L. Ultra-structural studies on the localization of IgG in the aortic endothelium and subendothelial intima of atherosclerotic and non-atherosclerotic rabbits. Exp. Mol. Path. 33: 301 (1980).CrossRefGoogle Scholar
  17. Hansson, G. K., Björnheden, T., Bylock, A., and Bondjers, G. Fc-dependent binding of monocytes to areas with endothelial injury in the rabbit aorta. Exp. Mol. Path. 34: 264 (1981).CrossRefGoogle Scholar
  18. Hansson, G. K., Starkebaum, G. A., Benditt, E. P., and Schwartz, S. M. Fc-mediated binding of IgG to vimentin-type intermediate filaments in vascular endothelial cells. Proc. Natl. Acad. Sci. 81: 3103 (1984).PubMedCrossRefGoogle Scholar
  19. Hansson, G. K., Lagerstedt, E., Bengtsson, A., and Heideman, M. IgG binding to cytoskeletal intermediate filaments activates the complement cascade. Exp. Cell Res. 170: 338 (1987).PubMedCrossRefGoogle Scholar
  20. Hugod, C, Hawkins, L. H., Kjeldsen, K., Thomsen, H. K. and Astrup, P. Effect of carbon monoxide exposure on aortic and coronary intimal morphology in the rabbit. Atherosclerosis 30: 333 (1978).PubMedCrossRefGoogle Scholar
  21. Kaplan, J. R., Manuck, S. B., Clarkson, T. B., Lusso, F.M., Taub, D. B. and Miller, E. W. Social stress and atherosclerosis in normo-cholesterolemic monkeys. Science 220: 733 (1983).PubMedCrossRefGoogle Scholar
  22. Kaplan, J. R., Manuck, S. B., Adams, M. R., Weingard, K. W., and Clarkson, T. B. Inhibition of coronary atherosclerosis by propranolol in behaviourally predisposed monkeys fed an atherogenic diet. Circulation 76: 1364 (1987).PubMedCrossRefGoogle Scholar
  23. Kjeldsen, K., and Thomsen, H. K. The effect of hypoxia on the fine structure of the aortic intima in rabbits. Lab. Invest. 33: 533 (1975).PubMedGoogle Scholar
  24. Manuck, S. B., Kaplan, J. R., and Matthews, K. A. Behavioral antecedents of coronary heart disease and atherosclerosis. Arteriosclerosis 6: 2 (1986).PubMedCrossRefGoogle Scholar
  25. Östlund-Lindqvist, A. M., Lindqvist, P., Bräutigam, J., Olsson, G., Bondjers, G., and Nordborg, C. Effect of metoprolol on dietinduced atherosclerosis in rabbits. Arteriosclerosis 8: 40 (1988).PubMedCrossRefGoogle Scholar
  26. Pettersson, K., Bejne, B., Björk, H., Strawn, W. B. and Bondjers G. Experimental sympathetic activation causes endothelial injury in the rabbit thoracic aorta via beta1-adrenoceptor activation. Circulation Res. submitted (1990).Google Scholar
  27. Reidy, M. A reassessment of endothelial injury and arterial lesion formation. Lab. Invest. 53: 513 (1985).PubMedGoogle Scholar
  28. Reidy, M. A., and Schwartz, S. M. Endothelial regeneration. III. Time course of intimai changes after small defined injury to the rat aortic endothelium. Lab. Invest. 44: 301 (1981).PubMedGoogle Scholar
  29. Reidy, M. A., and Schwartz, S. M. Arterial endothelium — assessment of in vivo injury. Exp. Mol. Path. 41: 419 (1984).CrossRefGoogle Scholar
  30. Reidy, M. A., Harker, L. A., Yoshida, K., and Schwartz, S. M. Vascular injury: detection of focal endothelial denudation using indium111- labeled platelets. J. Clin. Invest. 49: 565 (1984).Google Scholar
  31. Ross, R. Atherosclerosis: A problem of the biology of the arterial wall cells and their interactions with blood components. Arteriosclerosis 1: 293 (1981).PubMedCrossRefGoogle Scholar
  32. Ross, R. The pathogenesis of atherosclerosis — an update. N. Engl. J. Med. 314: 488 (1986).PubMedCrossRefGoogle Scholar
  33. Rylander, R., and Hellstrom, P. A. Versatile cage for environmental protection housing of research animals. Lab. Animal Science, 23: 876 (1973).Google Scholar
  34. Schwartz, S. M., and Benditt, E. P. Aortic endothelial cell replication. Effects of age and hypertension in the rat. Circ. Res. 41: 248 (1977).PubMedGoogle Scholar
  35. Sieffert, G. F., Keown, K., and Moore, W. S. Pathologic effect of tobacco smoke inhalation on arterial intima. Surg. Forum 32: 333 (1981).Google Scholar
  36. Spohr, U. and Hoffman, W. Evaluation of smoking-induced effects on sympathetic, hemodynamic and metabolic variables with respect to plasma nicotine and COHb levels. Atherosclerosis 33: 271 (1979).PubMedCrossRefGoogle Scholar
  37. Stemerman, M. B., and Ross, R. Experimental arteriosclerosis I. Fibrous plaque formation in primates, an electron microscopic study. J. Exp. Med. 136: 769 (1972).PubMedCrossRefGoogle Scholar
  38. Strawn, W. B., Bondjers, G., Kaplan, J. R., Manuck, S. B., Hansson, G. K., and Clarkson, T. B. Psychosocial stress and endothelial integrity in Cynomolgus monkeys. In preparation (1990).Google Scholar
  39. Wikstrand, J., Warnold, I., Olsson, G., Tuomilehto, J., Elmfeldt, D., and Berglund, G. Primary prevention with metoprolol in patients with hypertension. Mortality results from the MAPHY. JAMA 259: 1976 (1988).PubMedCrossRefGoogle Scholar
  40. Virchow, R. Der ateromatose prozess der arterien. Wien Med. Wochenschr 6: 825 (1856).Google Scholar
  41. Zimmerman, M. J. and McGeachie, J. The effect of nicotine on aortic endothelium. A quantitative ultrastructural study. Atherosclerosis 63: 33 (1987)PubMedCrossRefGoogle Scholar
  42. Zimmerman, M. J. and McGeachie, J. The effect of nicotine on aortic endothelial cell turnover — an autoradiographic study. Atherosclerosis 58: 39 (1985).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Göran Bondjer
    • 1
  • Göran Hansson
    • 1
  • Gun Olsson
    • 1
  • Knut Pettersson
    • 1
  1. 1.Wallenberg Laboratory for Cardiovascular ResearchUniversity of GöteborgGöteborgSweden

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