Proliferation of Arterial Cells in Atherosclerosis

  • H. C. Stary
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 43)


The role of cell proliferation in atherosclerosis has received much attention. It has been suggested for many years that the increase in cells during the formation of intimal lesions may be due to intrinsic proliferation. This hypothesis was based mainly on the observation of mitotic figures in the smooth muscle and foam cells of atherosclerotic plaques, even though mitoses were seen only rarely. On the other hand, it was proposed but never definitely established that migration of cells from the circulation, endothelium or media accounts for the cellular growth of the lesions. Monocytes, endothelial cells, and medial smooth muscle cells thus have been implicated.


Smooth Muscle Cell Foam Cell Serum Cholesterol Level Tritiated Thymidine Fatty Streak 
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  1. Altschul, R. (1950). “Selected Studies on Arteriosclerosis.” 1st edition. Charles C Thomas, Springfield, Illinois.Google Scholar
  2. Anitschkow, N. (1928). Über die Rueckbildungsvorgaenge bei der experimentellen Atherosklerose. Verh. Deut. Pathol. Ges. 23, 473. Zentralbl. Allg. Pathol. Pathol. Anat., Suppl. 43.Google Scholar
  3. Armstrong, M.L., Warner, E.D., and Connor, W.E. (1970). Regression of coronary atheromatosis in rhesus monkeys. Circ. Res. 27, 59.PubMedGoogle Scholar
  4. Benditt, E.P., and Benditt, J.M. (1973). Evidence for a monoclonal origin of human atherosclerotic plaques. Proc. Nat. Acad. Sci. U.S.A. 70, 1753.CrossRefGoogle Scholar
  5. Caplan, B.A., and Schwartz, C.J. (1973). Increased endothelial cell turnover in areas of invivo Evans Blue uptake in the pig aorta. Atherosclerosis 17, 401.PubMedCrossRefGoogle Scholar
  6. Cavallero, C. (1971). The proliferative nature of atherosclerosis. In “The Artery and the Process of Arteriosclerosis: Pathogenesis.” (Stewart Wolf, ed.). Proceedings of the Conference on Reactions of Vascular Tissue in Man, Lindau, 1970. Adv. Exp. Med. Biol. 16A, 225. Plenum Press, New York.Google Scholar
  7. Cavallero, C., DiTondo, U., Mingazzini, P.L., Pesando, P.C., and Spagnoli, L.G. (1973). Cell proliferation in the atherosclerotic lesions of cholesterol-fed rabbits. Part 2. Histological, ultrastructural and radioautographic observations on epinephrine-treated rabbits. Atherosclerosis 17, 49.PubMedCrossRefGoogle Scholar
  8. Cavallero, C., Turolla, E., and Ricevuti, G. (1971). Cell proliferation in the atherosclerotic plaques of cholesterol-fed rabbits. Part 1. Colchicine and [3H]thymidine studies. Atherosclerosis 13, 9.PubMedCrossRefGoogle Scholar
  9. Crane, W.A.J., and Ingle, D.J. (1964). Tritiated thymidine uptake in rat hypertension. Arch. Pathol. 78, 209.PubMedGoogle Scholar
  10. Daoud, A.S., Fritz, K.E., and Jarmolych, J. (1970). Increased DNA synthesis in aortic explants from swine fed a high cholesterol diet. Exp. Mol. Pathol. 13, 377.PubMedCrossRefGoogle Scholar
  11. Duff, G.L., McMillan, G.C., and Lautsch, E.V. (1954). The uptake of colloidal thorium dioxide by the arterial lesions of cholesterol atherosclerosis in the rabbit. Amer. J. Pathol. 30, 941.Google Scholar
  12. Eggen, D.A., and Strong, J.P. (1970). Diet and cholesterol metabolism in young and old baboons. Atherosclerosis 12, 359.PubMedCrossRefGoogle Scholar
  13. Florentin, R.A., Nam, S.C., Janakidevi, K., Lee, K.T., Reiner, J.M., and Thomas, W.A. (1973). Population dynamics of arterial smooth muscle cells. II. In vivo inhibition of entry into mitosis of swine arterial smooth muscle cells by aortic tissue extracts. Arch. Pathol. 95, 317.PubMedGoogle Scholar
  14. Florentin, R.A., Nam, S.C., Lee, K.T., Lee, K.J., and Thomas, W.A. (1969a). Increased mitotic activity in aortas of swine. Arch. Pathol. 88, 463.PubMedGoogle Scholar
  15. Florentin, R.A., Nam, S.C., Lee, K.T., and Thomas, W.A. (1969b). Increased 3H-thymidine incorporation into endothelial cells of swine fed cholesterol for 3 days. Exp. Mol. Pathol. 10, 250.PubMedCrossRefGoogle Scholar
  16. French, J.E. (1966). Atherosclerosis in relation to the structure and function of the arterial intima, with special reference to the endothelium. Int. Rev. Exp. Pathol. 5, 253.PubMedGoogle Scholar
  17. Geer, J.C. (1965). Fine structure of canine experimental atherosclerosis. Amer. J. Pathol. 47, 241.Google Scholar
  18. Geer, J.C., McGill, H.C., Jr., Robertson, W.B., and Strong, J.P. (1968). Histologic characteristics of coronary artery fatty streaks. Lab. Invest. 18, 565.PubMedGoogle Scholar
  19. Hassler, O. (1971). Arterial cell renewal under hyperlipidemic conditions. Virchows Arch. Abt. A. 352, 26.CrossRefGoogle Scholar
  20. Imai, H., Lee, K.T., Pastori, S., Panlilio, E., Florentin, R., and Thomas, W.A. (1966). Atherosclerosis in rabbits. Architectural and subcellular alterations of smooth muscle cells of aortas in response to hyperlipemia. Exp. Mol. Pathol. 5, 273.PubMedCrossRefGoogle Scholar
  21. Kao, V.C.Y., Wissler, R.W., and Dzoga, K. (1968). The influence of hyperlipemic serum on the growth of medial smooth muscle cells of rhesus monkey aorta in vitro. Circulation 38 (Suppl. 6), 12.Google Scholar
  22. Kramsch, D.M., Hollander, W., and Franzblau, C. (1972). Suppression of fibrous plaque formation by a connective tissue inhibitor (penicillamine) and by an antimitotic agent (colchicine). Circulation 46 (Suppl. 2), 254.Google Scholar
  23. Kritchevsky, D., Tepper, S.A., Vesselinovitch, D., and Wissler, R.W. (1971). Cholesterol vehicle in experimental atherosclerosis. Part II. Peanut Oil. Atherosclerosis 14, 53.PubMedCrossRefGoogle Scholar
  24. Kunz, J., Kranz, D., and Keim, O. (1967). Effect of hydrocortisone acetate on cell metabolism in experimental intima proliferation of rat aorta. Virchows Arch. Pathol. Anat. 342, 353.CrossRefGoogle Scholar
  25. Kunz, J., Sajkiewicz, K., Kranz, D., Fuhrmann, I., Bausdorf, B., and Keim, U. (1971). Intimal proliferation in the rat aorta in experimental diabetes mellitus. Exp. Pathol. 5, 78.Google Scholar
  26. Marshall, J.R., Adams, J.G., O’Neal, R.M., and DeBakey, M.E. (1966). The ultrastructure of uncomplicated human atheroma in surgically resected aortas. J. Atheroscler. Res. 6, 120.PubMedCrossRefGoogle Scholar
  27. McMillan, G.C., and Duff, G.L. (1948). Mitotic activity in the aortic lesions of experimental atherosclerosis in rabbits. Arch. Pathol. 46, 179.Google Scholar
  28. McMillan, G.C., and Stary, H.C. (1968a). Preliminary experience with mitotic activity of cellular elements in the atherosclerotic plaques of cholesterol-fed rabbits studied by labeling with tritiated thymidine. Ann. N.Y. Acad. Sci. 149, 699.PubMedCrossRefGoogle Scholar
  29. McMillan, G.C., and Stary, H.C. (1968b). Radioautographic observations on DNA synthesis in the cells of arteriosclerotic lesions of cholesterol fed rabbits. In “Recent Advances in Atherosclerosis.” Proceedings of the International Symposium on Atherosclerosis, Athens, 1966. Progr. Biochem. Pharmacol. 4, 280–281, S. Karger, Basel.Google Scholar
  30. Murata, K. (1967). Tritiated thymidine incorporation into aortic cells in vivo; cell regeneration in spontaneous atherosclerosis in monkeys. Experientia 23, 732.PubMedCrossRefGoogle Scholar
  31. Myasnikov, A.L., and Block, Y.E. (1965). Influence of some factors on lipoidosis and cell proliferation in aorta tissue cultures of adult rabbits. J. Atheroscler. Res. 5, 33.PubMedCrossRefGoogle Scholar
  32. Poole, J.C.F. (1964). Regeneration of aortic tissues in fabric grafts of the aorta. In “Cardiovascular Anatomy and Pathology.” (R.G. Harrison and K.R. Hill, eds.). Symposia of the Zoological Society of London, Vol. 11, 131. The London Society.Google Scholar
  33. Prior, J.T., and Ziegler, D.D. (1965). Regression of experimental atherosclerosis. Arch. Pathol. 80, 50.Google Scholar
  34. Robertson, A.L. (1965). Metabolism and ultrastructure of the arterial wall in atherosclerosis. Cleveland Clin. Quart. 32, 99.PubMedGoogle Scholar
  35. Robertson, A.L. (1971). The proliferative nature of atherosclerosis: adaptive and reparative. In “The Artery and the Process of Arteriosclerosis: Pathogenesis.” (Stewart Wolf, ed.). Proceedings of the Conference on Reactions of Vascular Tissue in Man, Lindau, 1970. Adv. Exp. Med. Biol. 16A, 104–107; 229–238. Plenum Press, New York.Google Scholar
  36. Ross, R. (1971a). The smooth cell. I. In vivo muscle of connective tissue synthesis J. Cell Biol. proteins. 50, 159.CrossRefGoogle Scholar
  37. Ross, R. (1971b). The smooth muscle cell. II. Growth of smooth of muscle in culture and formation elastic fibers. J. Cell Biol. 50, 172.CrossRefGoogle Scholar
  38. Schmitt, G., Knoche,. H., Junge-Huelsing, G., Koch, R., and Hauss, W.H. (1970). liber die Reduplikation von Aortenwandzellen bei arterieller Hypertonie. Z. Kreislaufforsch. 59, 481.PubMedGoogle Scholar
  39. Schwartz, S.M., and Benditt, E.P. (1973). Cell replication in the aortic endothelium; a new method for study of the problem. Lab. Invest. 28, 699.PubMedGoogle Scholar
  40. Spaet, T.H., and Lejnieks, I. (1967). Mitotic activity in rabbit blood vessels. Proc. Soc, Exp. Biol. Med. 125, 1197.Google Scholar
  41. Spraragen, S.C., Bond, V.P., and Dahl, L.K. (1962). Role of hyperplasia in vascular lesions of cholesterol fed rabbits studied with thymidine-H3 autoradiography. Circ. Res. 11, 329.PubMedGoogle Scholar
  42. Spraragen, S.C., Giordano, A.R., Poon, T.P., and Hamel, H. (1969). Participation of circulating mononuclear cells in the genesis of atheromata. Circulation 40 (Suppl. 3), 24.Google Scholar
  43. Stary, H.C. (1967). Cell proliferation in the experimental atheroma as revealed by radioautography after injection of thymidine-H3. Circulation 36 (Suppl. II), 39.Google Scholar
  44. Stary, H.C. (1970). Electron microscopic observations on the progression of aortic atherosclerosis in rhesus monkeys. Circulation 42 (Suppl. 3), 9.Google Scholar
  45. Stary, H.C. (1973). Electron microscopic observations on the progression of coronary atherosclerosis in rhesus monkeys. Amer. J. Pathol. 70, 39a.Google Scholar
  46. Stary, H.C. (1972). Progression and regression of experimental atherosclerosis in rhesus monkeys. In “Medical Primatology, 1972.” Proceedings of the 3rd Conference on Experimental Medicine and Surgery in Primates, Lyon, 1972. Part III, pp. 356–367. S. Karger, Basel.Google Scholar
  47. Stary, H.C. (In Press). Cell proliferation and ultrastructural changes in regressing atherosclerotic lesions after reduction of serum cholesterol. In “Atherosclerosis.” Proceedings of the 3rd International Symposium, Berlin, 1973. Springer, New York.Google Scholar
  48. Stary, H.C. (1969). Radioautographic observations on DNA synthesis of aortic cells in rhesus monkeys. Circulation 40 (Suppl. 3), 25.Google Scholar
  49. Stary, H.C., and McMillan, G.C. (1970). Kinetics of cellular proliferation in experimental atherosclerosis. Arch. Pathol. 89, 173.PubMedGoogle Scholar
  50. Stary, H.C., and Strong, J.P. (In press). Coronary artery fine structure in rhesus monkeys: nonatherosclerotic intimal thickening. In “Atherosclerosis in Primates” (J.P. Strong, ed,). Prim. Med., S. Karger, Basel.Google Scholar
  51. Stary, H.C., Strong, J.P., and Eggen, D.A. (1968). (Unpublished observations).Google Scholar
  52. Still, W.J.S. (1963). An electron microscope study of cholesterol atherosclerosis in the rabbit. Exp. Mol. Pathol. 2, 491.CrossRefGoogle Scholar
  53. Thomas, W.A., Florentin, R.A., Nam, S.C., Kim, D.N., Jones, R.M. and Lee, K.T. (1968). Preproliferative phase of atherosclerosis in swine fed cholesterol. Arch. Pathol. 86, 621.PubMedGoogle Scholar
  54. Wegener, K. (1973). (Personal Communication).Google Scholar
  55. Wissler, R.W., Vesselinovitch, D., Getz, G.S., and Hughes, R.H. (1967). Aortic lesions and blood lipids in rhesus monkeys fed three food fats. Fed. Proc. 26, 371.Google Scholar
  56. Wright, H.P. (1968). Endothelial mitosis around aortic branches in normal guinea-pigs. Nature (London) 220, 78.CrossRefGoogle Scholar
  57. Zahn, F.W. (1884). Untersuchung über die Vernarbung von Querrissen der Arterienintima und Media nach vorheriger Umschnuerung. Virchows Arch. Pathol. Anat. 96, 1.Google Scholar
  58. Zollinger, H.U. (1967). Adaptive Intimafibrose der Arterien. Virchows Arch. Pathol. Anat. 342, 154.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1974

Authors and Affiliations

  • H. C. Stary
    • 1
  1. 1.Department of PathologyLouisiana State University School of MedicineNew OrleansUSA

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