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The Comparative Pathology of Nonhuman Primate Atherosclerosis

  • Thomas B. Clarkson
  • Mary S. Anthony
  • Robert W. Prichard

Abstract

The ideal animal model for atherosclerosis research would develop the lesions gradually during its lifetime and would develop clinical manifestations of the disease in late middle and old age. The atherosclerotic lesions of the ideal model would range from trivial abnormalities, such as fatty streaks, found only at necropsy, to raised plaques with complications such as ulceration, stenosis, hemorrhage and superimposed thrombosis. The number of animals developing such complicated lesions would ideally constitute about 20% of the population, with males developing complications more frequently than females, particularly in the coronary arteries. The clinically-significant lesions would be found first in the aorta, later in the coronary arteries and later still in the arteries supplying the brain. The end-organ complications of myocardial and cerebral infarction and gangrene of the extremities would be seen. Aneurysm formation in the aorta would develop occasionally. All of these things should take place in an animal sufficiently large to allow diagnostic and therapeutic measurements similar to those useful for human beings.

Keywords

Rhesus Monkey Cynomolgus Monkey African Green Monkey Fatty Streak Vervet Monkey 
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References

  1. 1.
    T. B. Clarkson, N. D. M. Lehner, B. C. Bullock, H. B. Lofland, and W. D. Wagner, Atherosclerosis in New World monkeys, Primates Med. 9: 90 (1976).Google Scholar
  2. 2.
    C. C. Middleton, T. B. Clarkson, H. B. Lofland, and R. W. Prichard, Atherosclerosis in the squirrel monkey. Naturally-occurring lesions of the aorta and coronary arteries, Arch. Pathol. 78: 16 (1964).Google Scholar
  3. 3.
    C. C. Middleton, J. Rosal, T. B. Clarkson, W. P. Newman, III, and H. C. McGill, Jr., Arterial lesions in squirrel monkeys, Arch. Pathol. 83: 352 (1967).Google Scholar
  4. 4.
    T. B. Clarkson, R. B. Lofland, B. C. Bullock, and H. O. Goodman, Genetic control of plasma cholesterol. Studies on squirrel monkeys, Arch. Pathol. 92: 37 (1971).Google Scholar
  5. 5.
    B. C. Bullock, and J. Moossy, Cerebral infarction with atherosclerotic occlusion of the middle cerebral artery in a squirrel monkey (Saimiri sciureus), fed an atherogenic diet, J. Neuropath. Exp. Neurol 31: 177 (1972).Google Scholar
  6. 6.
    G. A. Boorman, S. Silverman, and J. H. Anderson, Spontaneous dissecting aortic aneurysm in a squirrel monkey (Saimiri sciureus), Lab. Animal Sci. 26: 942 (1976).Google Scholar
  7. 7.
    T. B. Clarkson, N. D. M. Lehner, B. C. Bullock, H. B Lofland, and W. D. Wagner, Atherosclerosis in New World monkeys, in: “Primates in Medicine,” J. P. Strong, ed., S. Karger, Basel (1976).Google Scholar
  8. 8.
    H. F. Stills, Jr., B. C. Bullock, Renal disease in squirrel monkeys (Saimiri sciureus), Vet. Pathol. 18: 38 (1981).Google Scholar
  9. 9.
    K. C. Hayes, N. P. Westmoreland, and T. P. Faherty, An aortitis in the squirrel monkey and its effect on atherosclerosis, Exp. Mol. Pathol. 17: 334 (1972).CrossRefGoogle Scholar
  10. 10.
    G. W. Melchior, H. B. Lofland, and R. W. St. Clair, The effect of polyunsaturated fats on bile acid metabolism and cholelithiasis in squirrel monkeys, Metabolism 27: 1471 (1978).CrossRefGoogle Scholar
  11. 11.
    O. W. Portman, M. Alexander, N. Tanaka, and T. Osuga, Relationship between cholesterol gallstones, biliary function, and plasma lipoproteins in squirrel monkeys, J. Lab. Clin. Med. 96: 90 (1980).Google Scholar
  12. 12.
    R. W. St. Clair, J. E. MacNintch, C. C. Middleton, T. B. Clarkson, and H. B Lofland, Changes in serum cholesterol levels of squirrel monkeys during importation and acclimation, Lab. Invest. 16: 828 (1967).Google Scholar
  13. 13.
    C. M. Lang, Effects of psychic stress on atherosclerosis in the squirrel monkey (Saimiri sciureus), Proc. Soc. Exp. Biol. Med. 126: 30 (1976).Google Scholar
  14. 14.
    J. S. Reitman, R. W. Mahley, and D. L. Fry, Yucatan miniature swine as a model for diet-induced atherosclerosis, Atherosclerosis 43: 119 (1982).CrossRefGoogle Scholar
  15. 15.
    C. B. Taylor, P. Manalo-Estrella, and C. E. Cox, Atherosclerosis in rhesus monkeys. V. Marked diet-induced hypercholesterolemia with xanthomatosis and severe atherosclerosis, Arch. Pathol. 76: 239 (1963).Google Scholar
  16. 16.
    C. B. Taylor, D. E. Patton, and G. E. Cox, Atherosclerosis in rhesus monkeys. VI. Fatal myocardial infarction in a monkey fed fat and cholesterol, Arch. Pathol. 76: 404 (1963).Google Scholar
  17. 17.
    L. L. Rudel, R. Shah, and D. H. Greene, Study of the atherogenic dyslipoproteinemia induced by dietary cholesterol in rhesus monkeys (Macaca mulatta), J. Lipid Res. 20: 55 (1979).Google Scholar
  18. 18.
    R. N. Chakravarti, A. P. Mohan, and H. S. Komal, Atherosclerosis in Macaca mulatta: histopathological, morphometrics, and histochemical studies in aorta and coronary arteries of spontaneous and induced atherosclerosis, Exp. Mol. Pathol. 25: 390 (1976).CrossRefGoogle Scholar
  19. 19.
    B. A. Lapin, and L. A. Yakoleva, “Comparative Pathology in Monkeys,” C. C. Thomas, Springfield (1963).Google Scholar
  20. 20.
    T. B. Clarkson, and N. J. Alexander, Long-term vasectomy. Effects on the occurrence and extent of atherosclerosis in rhesus monkeys, J. Clin. Invest. 65: 15 (1980).CrossRefGoogle Scholar
  21. 21.
    R. F. Scott, E. S. Morrison, J. Jarmolych, S. C. Nam, M. Kroms, F. Coulston, Experimental atherosclerosis in rhesus monkeys. I. Gross and light microscopy features and lipid values in serum and aorta, Exp. Mol. Pathol. 7: 11 (1967).CrossRefGoogle Scholar
  22. 22.
    R. F. Scott, R. Jones, A. S. Daoud, O. Zumbo, F. Coulston, and W. A. Thomas, Experimental atherosclerosis in rhesus monkeys. II. Cellular elements of proliferative lesions and possible role of cytoplasmic degeneration in pathogenesis as studied by electron microscopy, Exp. Mol. Pathol. 7: 34 (1967).CrossRefGoogle Scholar
  23. 23.
    P. J. Manning, and T. B. Clarkson, Development, distribution and lipid content of diet-induced atherosclerotic lesions of rhesus monkeys, Exp. Mol. Pathol. 17: 38 (1972).CrossRefGoogle Scholar
  24. 24.
    B. C. Bullock, W. D. Wagner, M. G. Bond, and T. B. Clarkson, The effect of intermittent hypercholesterolemia on aortic atherosclerosis of rhesus monkeys, Am. J. Pathol. 82: 82 (1976).Google Scholar
  25. 25.
    H. C. McGill, M. H. Frank, and J. C. Geer, Aortic lesions in hypertensive monkeys, Arch. Pathol. 71: 96 (1961).Google Scholar
  26. 26.
    D. S. Kim, Experimental production of arteriosclerosis in rhesus monkeys by deficiency of pyridoxine hydrochloride and essential fatty acids, Yonsei Med J. 1: 42 (1961).Google Scholar
  27. 27.
    J. F. Rinehart, and L. D. Greenberg, Arteriosclerotic lesions in pyridoxine deficient monkeys, Am. J. Pathol. 25: 481 (1949).Google Scholar
  28. 28.
    M. G. Bond, B. C. Bullock, D. A. Bellinger, and T. E. Hamm, Myocardial infarction in a large colony of nonhuman primates with coronary artery atherosclerosis, Am. J. Pathol. 101: 675 (1980).Google Scholar
  29. 29.
    M. L. Armstrong, E. D. Warner, and W. E. Connor, Regression of coronary atheromatosis in monkeys, Circ. Res. 27: 59 (1970).CrossRefGoogle Scholar
  30. 30.
    R. W. Wissler and D. Vesselinovitch, Studies of regression of advanced atherosclerosis in experimental animals and man, Ann. N. Y. Acad. Sci. 275: 36 (1976).CrossRefGoogle Scholar
  31. 31.
    D. A. Eggen, J. P. Strong, W. P. Newman, III, C. Catsulis, G. T. Malcom, M. G. Kokatnur, Regression of diet-induced fatty streaks in rhesus monkeys, Lab. Invest. 31: 294 (1974).Google Scholar
  32. 32.
    T. B. Clarkson, N. D. M. Lehner, W. D. Wagner, R. W. St. Clair, M. G. Bond, and B. C. Bullock, A study of atherosclerosis regression in Macaca mulatta. I. Design of experiment and lesion induction, Exp. Mol. Pathol. 30: 360 (1979).CrossRefGoogle Scholar
  33. 33.
    T. B. Clarkson, M. G. Bond, B. C. Bullock, and C. A. Marzetta, A study of atherosclerosis regression in Macaca mulatta. IV. Changes in coronary arteries from animals with atherosclerosis induced for 19 months and then regressed for 24 or 48 months at plasma cholesterol concentrations of 300 or 200 mg/dl, Exp. Mol. Pathol. 34: 345 (1981).CrossRefGoogle Scholar
  34. 34.
    R. Pick, P. J. Johnson, and G. Glick, Deleterious effects of hypertension on the development of aortic and coronary atherosclerosis in stumptail macaques (Macaca speciosa) on an atherogenic diet, Circ. Res. 35: 472 (1974).CrossRefGoogle Scholar
  35. 35.
    R. Pick, and G. Glick, Effects of propranolol, minoxidil, and Clofibrate on cholesterol-induced atherosclerosis in stumptail macaques (Macaca arctoides), Atherosclerosis 27: 71 (1977).CrossRefGoogle Scholar
  36. 36.
    B. C. Bullock, N. D. M. Lehner, T. B. Clarkson, M. A. Feldner, W. D. Wagner, and E. B Lofland, Comparative primate atherosclerosis. I. Tissue cholesterol concentration and pathologic anatomy, Exp. Mol. Pathol. 22: 151 (1975).CrossRefGoogle Scholar
  37. 37.
    W. D. Wagner, and T. B. Clarkson, Comparative primate atherosclerosis. II. A biochemical study of lipids, calcium, and collagen in atherosclerotic arteries, Exp. Mol. Pathol. 23: 96 (1975).CrossRefGoogle Scholar
  38. 38.
    W. J. Powers, C. J. Mathias, M. J. Welch, L. S. Sherman, B. A. Siegel, and T. B. Clarkson, Scintigraphic detection of platelet deposition in atherosclerotic macaques: A new technique for investigation of antithrombotic drugs, Thromb. Res. 25: 137 (1982).CrossRefGoogle Scholar
  39. 39.
    M. B. Stemerman, and R. Ross, Experimental arteriosclerosis. I. Fibrous plaque formation in primates, an electron microscopy study, J. Exp. Med. 136: 769 (1972).CrossRefGoogle Scholar
  40. 40.
    R. Ross, and L. Harker, Hyperlipidemia and atherosclerosis, Science 193: 1094 (1976).CrossRefGoogle Scholar
  41. 41.
    M. R. McMahan, A. L. Rhyne, H. B Lofland, and G. P. Sackett, Effects of sex, age, and dietary modification on plasma lipids and lipoproteins of Macaca nemestrina, Proc. Soc. Exp. Biol. Med. 164: 27 (1980).Google Scholar
  42. 42.
    M. G. Bond, B. C. Bullock, and T. B. Clarkson, Diet induced coronary atherosclerosis of pig-tailed macaques, Am. J. Pathol. 82: 68A (1976).Google Scholar
  43. 43.
    B. Lucke, Spontaneous cerebral lesions in monkeys — their significance in experimental pathology, Arch. Neurol. Psychiat. 10: 212 (1923).CrossRefGoogle Scholar
  44. 44.
    C. W. Leathers, M. G. Bond, and L. L. Rudel, Effects of ethanol on dyslipoproteinemia and coronary artery atherosclerosis in nonhuman primates, Circulation 57 & 58: II-77 (1978).Google Scholar
  45. 45.
    L. L. Rudel, C. W. Leathers, M. G. Bond, and B. C. Bullock, Dietary ethanol-induced modifications in hyperlipoproteinemia and atherosclerosis in nonhuman primates (Macaca nemestrina), Arteriosclerosis 1: 144 (1981).CrossRefGoogle Scholar
  46. 46.
    K. Prathap, Spontaneous aortic lesions in wild adult Malaysian long-tailed monkeys (Macaca irus), J. Pathol. 110: 135 (1973).CrossRefGoogle Scholar
  47. 47.
    K. Prathap, Diet-induced aortic atherosclerosis in Malaysian long-tailed monkeys (Macaca irus), J. Pathol. 115: 163 (1975).CrossRefGoogle Scholar
  48. 48.
    M. L. Armstrong, and M. B. Megan, Arterial fibrous proteins in cynomolgus monkeys after atherogenic and regression diets, Circ. Res. 36: 256 (1975).CrossRefGoogle Scholar
  49. 49.
    W. D. Wagner, R. W. St. Clair, and T. B. Clarkson, Angiochemical and tissue cholesterol changes in Macaca fascicularis fed an atherogenic diet for three years, Exp. Mol. Pathol. 28: 140 (1978).CrossRefGoogle Scholar
  50. 50.
    M. R. Malinow, P. McLaughlin, L. Papworth, H. Naito, L. Lewis, and W. P. McNulty, A model for therapeutic interventions on established coronary atherosclerosis in a nonhuman primate, Adv. Exp. Med. Biol. 67: 3 (1976).Google Scholar
  51. 51.
    D. M. Kramsch, and W. Hollander, Occlusive atherosclerotic disease of the coronary arteries in monkeys (Macaca irus) induced by diet, Exp. Mol. Pathol. 9: 1 (1968).CrossRefGoogle Scholar
  52. 52.
    M. L. Armstrong, and M. B. Megan, Arterial fibrous proteins in cynomolgus monkeys after atherogenic and regression diets, Circ. Res. 36: 256 (1975).CrossRefGoogle Scholar
  53. 53.
    D. J. Farrar, H. D. Green, M. G. Bond, W. D. Wagner, and R. A. Gobbee, Aortic pulse wave velocity, elasticity, and composition in a nonhuman primate model of atherosclerosis, Circ. Res. 43: 52 (1978).CrossRefGoogle Scholar
  54. 54.
    J. N. Angelo, B. C. Bullock, and T. B. Clarkson, Neuropathologic survey of cerebrovascular disease in nonhuman primates. Paper presented at the Third Meeting of the American Society of Primatologists, Winston-Salem, North Carolina (June 3–5, 1980).Google Scholar
  55. 55.
    N. J. Alexander, and T. B. Clarkson, Vasectomy increases the severity of diet-induced atherosclerosis in Macaca fascicularis, Science 201: 538 (1978).CrossRefGoogle Scholar
  56. 56.
    L. L. Rudel, and L. L. Pitts, II, Male-female variability in the dietary cholesterol-induced hyperlipoproteinemia of cynomolgus monkeys (Macaca fascicularis), J. Lipid Res. 19: 992 (1978).Google Scholar
  57. 57.
    T. E. Hamm, Jr., J. R. Kaplan, T. B. Clarkson, and B. C. Bullock, Effects of gender and social behavior on the development of coronary artery atherosclerosis on cynomolgus macaques, Atherosclerosis (In Press).Google Scholar
  58. 58.
    M. R. Adams, T. B. Clarkson, J. R. Kaplan, and D. R. Koritnik, Ovariectomy, social stress and coronary artery atherosclerosis in cynomolgus monkeys, Circulation (In Press).Google Scholar
  59. 59.
    J. R. Kaplan, S. B. Manuck, T. B. Clarkson, F. M. Lusso, and D. M. Taub, Social status, environment, and atherosclerosis in cynomolgus monkeys, Arteriosclerosis 2: 359 (1982).CrossRefGoogle Scholar
  60. 60.
    J. R. Kaplan, S. B. Manuck, T. B. Clarkson, F. M. Lusso, D. M. Taub, and E. W. Miller, Social stress and atherosclerosis in normocholesterolemic monkeys, Science 220: 733 (1983).CrossRefGoogle Scholar
  61. 61.
    M. R. Malinow, P. McLaughlin, H. K. Naito, L. A. Lewis, and W. P. McNulty, Effect of alfalfa meal on shrinkage (regression) of atherosclerotic plaques during cholesterol feeding in monkeys, Atherosclerosis 30: 27 (1978).CrossRefGoogle Scholar
  62. 62.
    M. R. Malinow, P. McLaughlin, W. P. McNulty, H. K. Naito, and L. A. Lewis, Treatment of established atherosclerosis during cholesterol feeding in monkeys, Atherosclerosis 31: 185 (1978).CrossRefGoogle Scholar
  63. 63.
    D. Vesselinovitch, and R. W. Wissler, Reversal of atherosclerosis: Comparison of nonhuman primate models, in: “Atherosclerosis V.,” A. M. Gotto Jr., L. C. Smith, and B. Allen, eds, Springer-Verlag, New York-Heidelberg-Berlin (1980).Google Scholar
  64. 64.
    W. Hollander, B. Kirkpatrick, J. Paddock, M. Colombo, S. Nagraj, and S. Prusty, Studies on the progression and regression of coronary and peripheral atherosclerosis in the cynomolgus monkey. I. Effects of dipyridamole and aspirin, Exp. Mol. Pathol. 30: 55 (1979).CrossRefGoogle Scholar
  65. 65.
    R. Pick, J. Chediak, and G. Glick, Aspirin inhibits development of coronary atherosclerosis in cynomolgus monkeys (Macaca fasicularis) fed an atherogenic diet, J. Clin. Invest. 63: 158 (1979).CrossRefGoogle Scholar
  66. 66.
    H. C. McGill Jr., C. A. McMahan, A. W. Kruski, G. E. Mott, Relationship of lipoprotein cholesterol concentrations to experimental atherosclerosis in baboons, Arteriosclerosis 1: 3 (1981).CrossRefGoogle Scholar
  67. 67.
    J. P. Strong, and H. C. McGill, Jr. Diet and experimental atherosclerosis in baboons, Am. J. Pathol. 50: 669 (1967).Google Scholar
  68. 68.
    H. C. McGill Jr., J. P. Strong, R. L. Holman, and N. Werthessen, Arterial lesions in the Kenya baboon, Circ. Res. 8: 670 (1960).CrossRefGoogle Scholar
  69. 69.
    J. P. Strong, D. A. Eggen, and S. K. Jirge, Atherosclerotic lesions produced in baboons by feeding an atherogenic diet for four years, Exp. Mol. Pathol. 24: 320 (1976).CrossRefGoogle Scholar
  70. 70.
    W. R. Rogers, R. L. Bass, III, D. E. Johnson, A. W. Kruski, C. A. McMahan, M. M. Montiel, G. E. Mott, R. L. Wilbur, and H. C. McGill, Jr. Atherosclerosis-related responses to cigarette smoking in the baboon, Circulation 61: 1188 (1980).CrossRefGoogle Scholar
  71. 71.
    L. L. Rudel, Plasma lipoproteins in atherogenesis in nonhuman primates, in: “The Use of Nonhuman Primates in Cardiovascular Diseases,” S. S. Kalter, ed., Univesity of Texas Press, Austin (1980).Google Scholar
  72. 72.
    L. L. Rudel, J. S. Parks, and R. M. Carroll, Effects of polyunsaturated versus saturated dietary fat on nonhuman primate HDL, in: “Dietary Fats and Health,” E. G. Perkins and W. J. Visek, eds, American Oil Chemists Society, Champaign (1983).Google Scholar
  73. 73.
    R. W. St. Clair, G. R. Henderson, V. Heaster, W. D. Wagner, M. G. Bond, and M. R. McMahan, Influence of dietary fats and an oral contraceptive on plasma lipids, high density lipoproteins, gallstones, and atherosclerosis in African green monkeys, Atherosclerosis 37: 103 (1980).CrossRefGoogle Scholar
  74. 74.
    B. C. Bullock, N. D. M. Lehner, T. B. Clarkson, M. A. Feldner, W. D. Wagner, and H. B Lofland, Comparative primate atherosclerosis. 1. Tissue cholesterol concentrations and pathologic anatomy, Exp. Mol. Pathol. 22: 151 (1975).CrossRefGoogle Scholar
  75. 75.
    W. D. Wagner, and T. B. Clarkson, Comparative primate atherosclerosis. II. A biochemical study of lipids, calcium, and collagen in atherosclerotic arteries, Exp. Mol. Pathol. 23: 96 (1975).CrossRefGoogle Scholar
  76. 76.
    T. B. Clarkson, Arteriosclerosis of African green and stump-tailed macaque monkeys, in: “Atherosclerosis III,” G. Schettler and A. Weizel, eds, Springer-Verlag, Berlin-Heidelberg-New York (1974).Google Scholar
  77. 77.
    A. A. Trillo, and R. W. Prichard, Early endothelial changes in experimental primate atherosclerosis, Lab. Invest. 41: 294 (1979).Google Scholar
  78. 78.
    A. A. Trillo. Formation of “ghost” bodies and calcification in experimental atherosclerosis in nonhuman primtes. An ultrastructural study, Virchovs Arch. [Cell Pathol.] 38: 127 (1981).CrossRefGoogle Scholar
  79. 79.
    A. A. Trillo, The cell population of aortic fatty streaks in African green monkeys with special reference to granulocytic cells. An ultrastructural study, Atherosclerosis 43: 259 (1982).CrossRefGoogle Scholar
  80. 80.
    D. Kritchevsky, L. M. Davidson, H. K. Kim, D. Krendel, and S. Malhotra, Influence of semipurified diet on atherosclerosis in African green monkeys, Exp. Mol. Pathol. 26: 28 (1977).CrossRefGoogle Scholar
  81. 81.
    D. Kritchevsky, L. M. Davidson, J. J. Van der Watt, P. A. D. Winter, and I. Bersohn, Hypercholesterolaemia and atherosclerosis induced in vervet monkeys by cholesterol-free, semisynthetic diets, S. Afr. Med. J. 48: 2413 (1974).Google Scholar
  82. 82.
    D. Kritchevsky, L. M. Davidson, H. K. Kim, and P. A. D. Winter, Lipid levels in serum, liver and aorta of the vervet monkey, J. Med. Primatol. 2: 242 (1973).Google Scholar
  83. 83.
    D. Kritchevsky, L. M. Davidson, D. A. Krendel, J. J. Van der Watt, D. Russel, S. Friedland and D. Mendelsohn, Influence of dietary fiber on aortic sudanophilia in vervet monkeys, Ann. Nutr. Metab. 25: 125 (1981).CrossRefGoogle Scholar
  84. 84.
    D. Kritchevsky, L. M. Davidson, M. Weight, N. P. J. Kriek, J. P. du Plessis, Influence of native and randomized peanut oil on lipid metabolism and aortic sudanophilia in the vervet monkey, Atherosclerosis 42: 53 (1982).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • Thomas B. Clarkson
    • 1
  • Mary S. Anthony
    • 1
  • Robert W. Prichard
    • 1
  1. 1.Arteriosclerosis Research Center, Bowman Gray School of MedicineWake Forest UniversityWinston-SalemUSA

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