Reversal of Atherosclerosis: Comparison of Non-Human Primate Models

  • D. Vesselinovitch
  • R. W. Wissler
Conference paper


Numerous reports attest to the usefulness of non-human primates for the study of experimental atherogenesis. During the past decade monkeys have also been utilized for investigations of lesion reversal (Wissler and Vesselinovitch 1977). Dietary regimens designed to reduce serum lipids as well as pharmacological and surgical interventions have been tested in six species. These include one new world species, the squirrel monkey (Saimuri sciureus), and five old world species, i.e., rhesus (Macaca mulatta), cynomolgus (Macaca fascicularis), stumptail (Macaca arctoides), African green monkeys (Cercopithecus aethiops), and baboon (Genus Papio). The approaches used thus far to influence the fate of experimentally induced atherosclerotic lesions are summarized in Table 1 (Armstrong and Megan 1974; Clarkson et al. 1979; De Palma et al. 1977; Hollander et al. 1979; Howard and Patelski 1974; Malinow et al. 1978; Maruffo and Portman 1968; Pick et al. 1978; Stary et al. 1977; Strong et al. 1977; Tucker et al. 1971; Vesselinovitch et al. 1979; Wissler 1979). Each of the primate models has shown special features of lesion configuration and composition during both induction and regression. The rhesus monkey has been the most widely studied (Armstrong and Megan 1974; Clarkson et al. 1979; Stary et al. 1977; Strong et al. 1977; Vesselinovitch et al. 1976; Wissler and Vesselinovitch 1977). Regression of “diet-induced” atherosclerosis in this species is characterized by a decrease in lipids and collagen within lesions as well as resolution of both necrosis and calcification. These regressive or healing changes are associated with a substantial reduction in degree of lumen obstruction. Although the lesions may be reduced readily by any one of several regimens, induction of severe coronary artery atherosclerosis appears to require specially severe atherogenic regimens for extended periods and/or special ancillary models of vessel injury. Lesions induced in the cynomolgus differ from those noted in the rhesus or in humans. In the cynomolgus large numbers of foam cells accumulate in the media and adventitia in association with marked fibroplasia and calcification. Intimal lesions are similar in composition and appear to heal after therapy, but there is little associated reduction of luminal narrowing of affected coronary or peripheral arteries (Hollander et al. 1979; Vesselinovitch and Wissler 1979). In contrast to the rhesus, however, induction of severe coronary artery lesions in the cynomolgus can be achieved in a relatively short time and may result in cardiovascular complications similar to those seen in man. These include coronary stenosis (M Kramsh 1979, personal communication) and development of severe cerebral artery atherosclerosis (Malinow et al. 1978). Lesion regression in the cynomolgus includes decrease of cholesterol content and disappearance of foam cells from the vessel wall. It may be speculated that great preponderance of “foam cells” represents a different cellular pathogenesis which results in a lesion type that is much less responsive to regression by means of serum cholesterol reduction. Despite the dissimilarities from human disease, the cynomolgus model would appear to be useful for the study of matrix protein in lesion regression and for the study of the role of calcium in lesion histogenesis (Armstrong and Megan 1974; Hollander et al. 1979).


Rhesus Monkey Foam Cell Squirrel Monkey African Green Monkey Coronary Artery Lesion 
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  1. Abell IL, Levy BB, Bradie BB, Kendall FB (1952) A simplified method for the estimation of total cholesterol in serum and demonstration of its specificity. J Biol Chem 195: 375.Google Scholar
  2. Armstrong ML, Megan MB (1974) Responses of two macaque species to athero-genic diet and its withdrawal. In: Schettler G., Weizel A (eds) Atherosclerosis III. Springer-Verlag, Berlin, p 336.CrossRefGoogle Scholar
  3. Bullock, BC, Clarkson TB, Lehner NDM, Lofland HB, St. Clair RW (1969) Atherosclerosis in Cebus albifrons monkeys III. Clinical and pathological studies. Exp Mol Pathol 10: 39.PubMedCrossRefGoogle Scholar
  4. Clarkson TB, Lehner NDM, Wagner WD, St. Clair RW, Bond MG, Bullock, BC (1979) A study of atherosclerosis regression in Macaca mulatta. I. Design of experiment and lesion induction. Exp Mol Pathol 30: 360.PubMedCrossRefGoogle Scholar
  5. DePalma RG, Bellon EM, Klein L, Koletsky S, Insull W Jr (1977) Approaches to evaluating regression of experimental atherosclerosis. Adv Exp Med Biol 82: 459.Google Scholar
  6. Hollander W, Kirkpatric B, Paddock J, Colombo M, Nagraj S, Prust S (1979) Studies on the progression and regression of coronary and peripheral atherosclerosis in the cynomolgus monkey. Exp Mol Pathol 30: 55.PubMedCrossRefGoogle Scholar
  7. Howard AN, Patelsk J (1974) Hydrolysis and synthesis of aortic cholesterol esters in atherosclerotic baboons. Effect of polyunsaturated phosphatidyl choline on enzyme activities. Atherosclerosis 20: 225.PubMedCrossRefGoogle Scholar
  8. Malinow RM, McLaughlin P, Naito WH, Lewis LA, McNulty WP (1978) Effect of alfalfa meal on shrinkage (regression) of atherosclerotic plaques during cholesterol feeding in monkeys. Atherosclerosis 30: 27.PubMedCrossRefGoogle Scholar
  9. Maruffo CA, Portman OW (1968) Nutritional control of coronary artery atherosclerosis in the squirrel monkey. J Atheros Res 8: 237.CrossRefGoogle Scholar
  10. Noble RP (1968) The electrophoretic separation of plasma lipoproteins in agarose gel. J Lipid Res 9: 963.Google Scholar
  11. Pick R, Prabhu R, Glic G (1978) Diet-induced atherosclerosis and experimental hypertension in stumptail macaques (Macaca arctoides). Effects of antihypertensive drugs and a non-atherogenic diet in the evaluation of lesions. Atherosclerosis 29: 405.PubMedCrossRefGoogle Scholar
  12. Stary HC, Eggen DA, Strong JP (1977) The mechanism of atherosclerosis regression. In: Schettler G, Goto Y, Hata Y, Cose GK (eds) Atherosclerosis IV. Springer-Verlag, Berlin, pp 394–404Google Scholar
  13. Strong JP, Stary HC, Eggen DA (1977) Evolution and regression of aortic fatty streaks in Rhesus monkeys. In: Atherosclerosis: Metabolic morphological and clinical aspects. Adv Exp Mol Med 82: 915.Google Scholar
  14. Tucker CF, Catsulis C, Strong JP, Eggen DA (1971) Regression of early cholesterol-induced aortic lesions in Rhesus monkeys. Am J Pathol 65: 493.PubMedGoogle Scholar
  15. Vesselinovitch D, Wissler RW, Hughes R, Borensztaj J (1976) Reversal of advanced atherosclerosis in Rhesus monkeys. I. Gross and light microscopic studies. Atherosclerosis 23: 155.CrossRefGoogle Scholar
  16. Vesselinovitch D, Wissler RW, Harri L (1979) The relationship between lipo-protein profiles and xanthomata in three species of non-human primates during development and regression of atherosclerosis. Fed Proc 38: 1347.Google Scholar
  17. Vesselinovitch D, Wissler RW, Schaffner TJ (1979) Quantitation of lesions during progression and regression of atherosclerosis in Rhesus monkeys. In: Cardiovascular disease in nutrition, Symposium of American College of Nutrition. Spectrum Publications, New York. In press.Google Scholar
  18. Wissler RW (1979) Evidence for regression of advanced atherosclerotic plaques. Artery 5(5): 398.PubMedGoogle Scholar
  19. Wissler RW, Vesselinovitc D (1977) Atherosclerosis in nonhuman primates. In: Advances in Veterinary Science and Comparative Medicine Vol 21. Academic Press, New York, p 351.Google Scholar

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© Springer-Verlag New York Inc. 1980

Authors and Affiliations

  • D. Vesselinovitch
  • R. W. Wissler

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