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Endothelial Injury and Atherosclerosis

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Endothelial Cell Biology in Health and Disease

Abstract

In 1973, we proposed a hypothesis of atherogenesis35 that provided a basis for the design of in vivo and in vitro experiments to determine how the advanced proliferative smooth muscle lesions of atherosclerosis form. Three fundamental biologic phenomena comprise the advanced lesions of atherosclerosis and lead to the development of occlusive lesions. Understanding why and how each of these phenomena occurs is fundamental to the development of this hypothesis. These phenomena are: (1) the accumulation of large numbers of intimal cells, principally proliferated smooth muscle together with numerous macrophages derived from blood monocytes; (2) formation by the proliferated smooth muscle cells of connective tissue matrix macromolecules including collagen, elastic fibers, and proteoglycans; and (3) accumulation of lipid both within the accumulated smooth muscle cells and macrophages, and within the components of the extracellular matrix. Any hypothesis of atherogenesis must take into account these phenomena, and should afford the opportunity to devise experiments to test the various components of the hypothesis

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References

  1. Assoian, R. K., and Sporn, M. B., 1986, Type p transforming growth factor in human platelets: Release during platelet degranulation and action on vascular smooth muscle cells, J. Cell. Biol. 102:1217–1223.

    Article  PubMed  CAS  Google Scholar 

  2. la. Assoian, R. K., Fleurdelys, B. E., Stevenson, H. C., Miller, P. J., Madtes, D. K., Raines, E. W., Ross, R., and Sporn, M. D., 1987, Expression and secretion of type (3 transforming growth factor by activated human macrophages, Proc. Nat. Acad. Sci. USA 84:6020-6024.

    Google Scholar 

  3. Baird, A., Morm£de, P., and Bohlen, P., 1985,Immunoreactive fibroblast growth factor in cells of peritoneal exudate suggests its identity with macrophage-derived growth factor, Biochem. Biophys. Res. Commun. 126:358–364.

    Article  PubMed  CAS  Google Scholar 

  4. Barrett, T. B., Gajdusek, C. M., Schwartz, S. M., McDougall, J. K., and Benditt, E. P., 1984, Expression of the sis gene by endothelial cells in culture and in vivo, Proc. Natl. Acad. Sci. USA 81:6772-6774.

    Google Scholar 

  5. Baumgartner, H. R., and Studer, A., 1966, Folgen des gefasskatheterismus am normo-und hypercholesterinaemischen kaninchen, Pathol. Microbiol. 29:393–405.

    CAS  Google Scholar 

  6. Bevilacqua, M. P., Pober, J. S., Cotran, R. S., and Gimbrone, M. A., Jr., 1985, Interleukin 1 (IL-1) acts upon vascular endothelium to stimulate procoagulant activity and leukocyte adhesion, J. Cell. Biochem. Suppl. 9A:148 (abstract).

    Google Scholar 

  7. Bitteman, P. B., Rennard, S. I., Hunninghake, G. W., and Crystal, R. G., 1982, Human alveolar macrophage growth factor for fibroblasts: Regulation and partial characterization, J. Clin. Invest. 70:806–822.

    Article  Google Scholar 

  8. Cathcart, M. K., Morel, D. W., and Chisolm, G. M., III, 1985, Monocytes and neutrophils oxidize low-density lipoprotein making it cytotoxic, J. Leukocyte Biol. 38:341–350.

    PubMed  CAS  Google Scholar 

  9. Chobanian, A. V., Brecher, P. I., and Haudenshild, C. C., 1986, Effects of hypertension and of antihypertension therapy on atherosclerosis: State of the Art Lecture, in: Inter-American Society Proceedings, Suppl. I 8:15–21.

    Google Scholar 

  10. DiCorleto, P. E., and Bowen-Pope, D. F., 1983, Cultured endothelial cells produce a plateletderived growth factor-like protein, Proc. Natl. Acad. Sci. USA 80:1919-1923.

    Google Scholar 

  11. DiCorleto, P. E., and de la Motte, C. A., 1985, Characterization of the adhesion of the human monocytic cell line U-937 to cultured endothelial cells, J. Clin. Invest. 75:1153–1161.

    Article  PubMed  CAS  Google Scholar 

  12. Dinarello, C. A., 1984, Interleukin-1, Rev. Infect. Dis. 6:51–95.

    Article  PubMed  CAS  Google Scholar 

  13. Faggiotto, A., and Ross, R., 1984, Studies of hypercholesterolemia in the nonhuman primate. II. Fatty streak conversion to fibrous plaque, Arteriosclerosis 4:341–356.

    Article  PubMed  CAS  Google Scholar 

  14. Faggiotto, A., Ross, R., and Harlan, L., 1984, Studies of hypercholesterolemia in the nonhuman primate. I. Changes that lead to fatty streak formation, Arteriosclerosis 4:323–340.

    Article  PubMed  CAS  Google Scholar 

  15. Gajdusek, C., DiCorleto, P., Ross, R., and Schwartz, S. M., 1980, An endothelial cell-derived growth factor, Cell. Biol. 85:467–472.

    Article  CAS  Google Scholar 

  16. Gerrity, R. G., 1981, The role of the monocyte in atherogenesis. I. Transition of blood borne monocytes into foam cells in fatty lesions, Am. J. Pathol. 103:181–190.

    PubMed  CAS  Google Scholar 

  17. Gerrity, R. G., 1981, The role of the monocyte in atherogenesis. II. Migration of foam cells from atherosclerotic lesions, Am. J. Pathol. 103:191–200.

    PubMed  CAS  Google Scholar 

  18. Glenn, K. C., and Ross, R., 1981, Humn monocyte-derived growth factor(s) for mesenchymal cells: Activation of secretion by endotoxin and concanavalin A, Cell 25:603–615.

    Article  PubMed  CAS  Google Scholar 

  19. Harker, L. A., Ross, R., Slichter, S. J., and Scott, C. R., 1976, Homocystine-induced atherosclerosis: The role of endothelial cell injury and platelet response in its genesis,J. Clin. Invest. 58:731–741.

    Article  PubMed  CAS  Google Scholar 

  20. Heldin, C.-H., and Westermark, B., 1984, Growth factors: mechanism of action and relation to oncogenes, Cell 37:9–20.

    Article  PubMed  CAS  Google Scholar 

  21. Jerome, W. G., and Lewis, J. C., 1984, Early atherogenesis in White Carneau pigeons. I. Leukocyte margination and endothelial alterations at the celiac bifurcation, Am. J. Pathol. 116:56–68

    PubMed  CAS  Google Scholar 

  22. Joris, J., Zand, T., Nunnary, J. L., Krolikowski, F. J., and Majno, G., 1983, Studies on the pathogenesis of atherosclerosis. I. Adhesion and emigration of mononuclear cells in the aorta of hypercholesterolemic rats, Am. J. Pathol. 113:341–358.

    PubMed  CAS  Google Scholar 

  23. Kohler, N., and Lipton, A., 1974, Platelete as a source of fibroblast growth-promoting activity, Exp. Cell Res. 87:297–301.

    Article  PubMed  CAS  Google Scholar 

  24. Leibovich, S. J., and Ross, R., 1976, A macrophage-dependent factor that stimulates the proliferation of fibroblasts in vitro, Am. J. Pathol. 84:501–513.

    PubMed  CAS  Google Scholar 

  25. Lewis, J. C., Taylor, R. G., Jones, N. D., St. Clair, R. W., and Cornhill, J. R., 1982, Endothelial surface characteristics in pigeon coronary artery atherosclerosis. I. Cellular alterations during the initial stages of dietary cholesterol challenge, Lab. Invest. 46:123–138.

    PubMed  CAS  Google Scholar 

  26. Madtes, D. K., Raines, E. W., Sakariassen, K. S., Assoian, R. K., Sporn, M. B., Bell, G. I., and Ross, R. 1988, Induction of transforming growth factor alpha in activated human alveolar macrophages, Cell (in press).

    Google Scholar 

  27. Martin, B. M., Gimbrone, M. A., Unanue, E. R., and Cotran, R. S., 1981, Stimulation of nonlymphoid mesenchymal cell proliferation by a macrophage-derived growth factor, J. Immunol. 126:1510–1515.

    PubMed  CAS  Google Scholar 

  28. Martinet, Y., Bitterman, P. B., Mornex, J.-F., Grotendorst, G. R., Martin, G. R., and Crystal, R. G., 1986,Activated human monocytes express the c-sis proto-oncogene and release a mediator showing PDGF-like activity, Nature 319:158–160.

    Article  PubMed  CAS  Google Scholar 

  29. Mazzone, T., Jensen, M., and Chait, A., 1983, Human arterial wall cells secrete factors that are chemotactic for monocytes, Proc. Natl. Acad. Sci. USA 80:5094-5097.

    Google Scholar 

  30. Nathan, C. F., Murray, H. W., and Cohn, Z. A., 1980, Current concepts: The macrophage as an effector cell, N. Engl. J. Med. 303:622–626.

    Article  PubMed  CAS  Google Scholar 

  31. Nilsson, J., Sjolund, M., Palmberg, L., Thyberg, J., and Heldin, C.-H., 1985, Arterial smooth muscle cells in primary culture produce a platelet-derived growth factor-like protein, Proc. Natl. Acad. Sci. USA 82:4418-4422.

    Google Scholar 

  32. Oka, Y., and Orth, D. N., 1983, Human plasma epidermal growth factor/p-urogastrone is associated with blood platelets, J. Clin. Invest. 72:249–259.

    Article  PubMed  CAS  Google Scholar 

  33. Report of the Working Group on Arteriosclerosis of the National Heart, Lung, and Blood Institute, 1981, Volume 2, Government Printing Office, Washington, D.C. [DHEW Publ. No. (NIH) 82-2035].

    Google Scholar 

  34. Rosenfeld, M. E., Faggiotto, A., and Ross, R., 1985, The role of the mononuclear phagocyte in primate and rabbit models of atherosclerosis, in: Proceedings of the Fourth Leiden Conference on Mononuclear Phagocytes, Nijhoff, The Hague, pp 795–802.

    Google Scholar 

  35. Ross, R., 1981, Atherosclerosis—A problem of the biology of arterial wall cells and their interaction with blood components, Arteriosclerosis 1:293–311.

    Article  PubMed  CAS  Google Scholar 

  36. Ross, R., 1986, The pathogenesis of atherosclerosis—An update, N. Engl. J. Med. 314:488–500.

    Article  PubMed  CAS  Google Scholar 

  37. Ross, R., and Glomset, J. A., 1973, Atherosclerosis and the smooth muscle cell, Science 180:1332–1339.

    Article  PubMed  CAS  Google Scholar 

  38. Ross, R., and Glomset, J. A., 1976, The pathogenesis of atherosclerosis, N. Engl. J. Med. 295:369–377, 420-425.

    Article  PubMed  CAS  Google Scholar 

  39. Ross, R., Glomset, J., Kariya, B., and Harker, L., 1974, A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro, Proc. Natl. Acad. Sci. USA 71:1207-1210.

    Google Scholar 

  40. Ross, R., and Harker, L., 1976, Hyperlipidemia and atherosclerosis, Science 193:1094–1100.

    Article  PubMed  CAS  Google Scholar 

  41. Ross, R., Raines, E. W., and Bowen-Pope, D. F., 1986, The biology of platelet-derived growth factor, Cell 46:155–169.

    Article  PubMed  CAS  Google Scholar 

  42. Ross, R., Wight, T. N., Strandness, E., and Theile, B., 1984, Human atherosclerosis. I. Cell constitution and characteristics of advanced lesions of the superficial femoral artery, Am. J. Pathol. 114:79–93.

    PubMed  CAS  Google Scholar 

  43. Seifert, R. A., Schwartz, S. M., and Bowen-Pope, D. F., 1984, Developmentally regulated production of platelet-derived growth factor-like molecules, Nature 311:669–671.

    Article  PubMed  CAS  Google Scholar 

  44. Shimokado, K., Raines, E. W., Madtes, D. K., Barrett, T. B., Benditt, E. P., and Ross, R., 1985, A significant part of macrophage-derived growth factor consists of at least two forms of PDGF, Cell 43:277–286.

    Article  PubMed  CAS  Google Scholar 

  45. Stemerman, M. B., and Ross, R., 1972, Experimental atherosclerosis. I. Fibrous plaque formation in primates, an electron microscope study, J. Exp. Med. 136:769–789.

    Article  PubMed  CAS  Google Scholar 

  46. Stiles, C. D., 1983, The molecular biology of platelet-derived growth factor, Cell 33:653–655.

    Article  PubMed  CAS  Google Scholar 

  47. Walker, L. N., Bowen-Pope, D. F., Ross, R., and Reidy, M. A., 1986, Production of PDGF-like molecules by cultured arterial smooth muscle cells accompanies proliferation after arterial injury, Proc. Natl. Acad. Sci. USA 83:7311-7315.

    Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, University of Washington, Seattle, Washington, 98195, USA

    Russell Ross

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  1. Russell Ross
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  1. Institute of Cellular Biology and Pathology, Bucharest, Romania

    Nicolae Simionescu  & Maya Simionescu  & 

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© 1988 Plenum Press, New York

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Ross, R. (1988). Endothelial Injury and Atherosclerosis. In: Simionescu, N., Simionescu, M. (eds) Endothelial Cell Biology in Health and Disease. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0937-6_17

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  • DOI: https://doi.org/10.1007/978-1-4613-0937-6_17

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4612-8254-9

  • Online ISBN: 978-1-4613-0937-6

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