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Monocytes and Susceptibility to Atherosclerosis

  • Ross G. Gerrity
  • Lynn E. Averill
Part of the NATO ASI Series book series (volume 166)

Abstract

In recent years, it has become increasingly clear that atherosclerotic lesions do not occur randomly in the arterial system. Rather, they have been shown to favor certain regions, while sparing others, both in the human (McGill, 1968a; McGill, 1968b; Mitchell and Schwartz, 1965) and in experimental models (Faggiotto and Ross, 1984; Gerrity et al., 1979; Jerome and Lewis, 1985; Joris et al., 1983). Modern computer-assisted image processing techniques have been developed to express the topographic distribution of lesions in statistical terms, thus quantifying precisely previous qualitative studies which have indicated that inflow tracts of ostia and flow dividers are particularly susceptible to early lesion development (Cornhill et al., 1985). Other studies have clarified the cellular composition of atherosclerotic plaques in both man (Geer et al., 1961; Ross et al., 1984) and animal models (Faggiotto and Ross, 1984; Gerrity et al., 1979, Jerome and Lewis, 1985; Joris et al., 1983; Faggiotto et al., 1984; Gerrity, 1981a; Gerrity, 1981b; Jerome and Lewis, 1984; Wissler and Vesselinovitch, 1977), and have provided insight into the relationships between cellular composition and lesion type, location, and progression. The fatty streak lesion (the earliest detectable form of atherosclerosis in man), is characteristically a lipid-rich, flat lesion consisting predominantly of macrophage foam cells with minimal smooth muscle cell involvement (McGill, 1968a). Advanced atherosclerosis in older individuals is more typified by various forms of fibrous plaques dominated by smooth muscle cells and enhanced amounts of connective tissue protein and matrix. The central core of such lesions consists of both intra- and extra-cellular lipid accumulations covered on the luminal aspect by a fibrous cap of smooth muscle and connective tissue. The question of whether the fatty streak is a precursor to the fibrous plaque has long been debated. However, recent data, reviewed by McGill (1968) supports the precursor concept, in that increased surface area coverage by fatty streaking precedes advanced plaques in coronary arteries. Stary (1985) has also shown that lesions in young children consist predominantly of macrophage-derived foam cells, with a few underlying lipid-laden smooth muscle cells. However, he also demonstrated advanced fibrous plaques at the same anatomical sites in older individuals, confirming earlier data (Geer et al., 1961; Robertson et al., 1963) which indicated an age-dependent relationship between fatty streaks and fibrous plaques at the same anatomical site. If, as these data would suggest, the fatty streak is indeed the precursor of the clinically-significant fibrous plaque, then the mechanisms controlling monocyte involvement in fatty streak initiation are of considerable importance, since the monocyte-derived foam cell is the predominant cell of the fatty streak. Furthermore, it has been demonstrated that one of the earliest events to occur in such lesion-susceptible areas is the large-scale recruitment of blood monocytes into the intima (Faggiotto and Ross, 1984; Gerrity et al., 1981a,b; Jerome and Lewis, 1985; Joris et al., 1983; Jerome and Lewis, 1984; Robertson et al., 1963).

Keywords

Bone Marrow Cell Foam Cell Evans Blue Lesion Formation Fatty Streak 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Adams, C.W., Bayliss, O.B., D.R., 1976, Detection of macrophages in atherosclerotic lesions with cytochrome oxidase, Br. J. Exp. Pathol., 57: 30.Google Scholar
  2. Adams, C.W., Bayliss, O.B., and Turner, D.R., 1975, Phagocytes, lipid-removal and regression of atheroma, J. Pathol., 116: 225.PubMedCrossRefGoogle Scholar
  3. Averill, L.E., Meagher, R.C., and Gerrity, R.G., 1988, Enhanced monocyte progenitor cell proliferation in bone marrow of hyperlipemic swine, In press, Amer. J. Pathol.Google Scholar
  4. Bar-Shavit, R., Kahn, A., Fenton, J.W., and Wilner, G.D., 1983, Chemotactic responses of monocytes to thrombin, J. Cell. Biol., 96: 282.PubMedCrossRefGoogle Scholar
  5. Becker, E.L., 1980, Chemotaxis, J. Allergy Clin. Immuno., 66: 97.CrossRefGoogle Scholar
  6. Bell, F.P., Adamson, I.L., and Schwartz, C.J., 1974a, Aortic endothelial permeability to albumin: Focal and regional patterns of uptake and transmural distribution of “I-albumin in the young pig, Exp. Mol. Pathol., 20: 57.PubMedCrossRefGoogle Scholar
  7. Bell, F.P., Gallus, A.S., and Schwartz, C.J., 1974b, Focal and regional patterns of uptake and the transmural distribution of 131I-fibrinogen in the pig aorta in vivo, Exp. Mol. Pathol., 20: 281.PubMedCrossRefGoogle Scholar
  8. Berliner, J.A., Territo, M., Almada, L., Carter, A., Shafonsky, E. and Fogelman, A.M., 1986, Monocyte chemotactic factor produced by large vessel endothelial cells in vitro, Arteriosclerosis, 6: 254.PubMedCrossRefGoogle Scholar
  9. Brown, M.S. and Goldstein, J.L., 1983, Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis, Ann. Rev. Biochem., 52: 223.PubMedCrossRefGoogle Scholar
  10. Burger, D.R. and Vetto, R.M., 1982, Hypothesis. Vascular endothelium as a major participant in T-lymphocyte immunity, Cell. Immunol., 70:357.PubMedCrossRefGoogle Scholar
  11. Chamley-Campbell, H.H., and Campbell, G.R., 1981, What controls smooth muscle phenotype?, Atherosclerosis,40:347.PubMedCrossRefGoogle Scholar
  12. Clarkson, T.B., 1963, Atherosclerosis spontaneous and induced, Adv. Lipid Res., 1:211. Clarkson, T.B. and Lofland, H.B., 1961, Effect of cholesterol-fat diet on pigeons susceptible to and resistant to atherosclerosis, Circ. Res., 9: 106.CrossRefGoogle Scholar
  13. Cornhill, J.F., Barrett, W.A., Herderick, E.E., Mahley, R.W. and Fry, D.L., 1985, Topographic study of sudanophilic lesions in cholesterol-fed minipigs by image analysis, Arteriosclerosis, 5: 415.PubMedCrossRefGoogle Scholar
  14. Daoud, A.J., Jarmolych, J., Augustyn, J.M. and Fritz, K.E., 1981 Sequential morphologic studies of regression of advanced atherosclerosis, Arch. Path. Lab. Med., 105: 233.PubMedGoogle Scholar
  15. Daoud, A.S., Fritz, K.E., Jarmolych, J. and Frank, A.S., 1985, Role of macrophages in regression of atherosclerosis, Ann. N.Y. Acad. Sci., 454: 101.PubMedCrossRefGoogle Scholar
  16. Day, A.J., 1963, Lipid metabolism by macrophages and its relationship to atherosclerosis, Adv. Lipid Res., 5: 185.Google Scholar
  17. Deuel, T.F., Senior, R.M., Haung, J.S., and Griffin, G.L., 1982, Chemotaxis of monocytes and neutrophils to platelet-derived growth factor, J. Clin. Invest., 69: 1046.PubMedCrossRefGoogle Scholar
  18. Dicorleto, P.E. and Bowen-Pope, D.R., 1983, Cultured endothelial cells produce a platelet derived growth factor-like portein, Proc. Natl. Acad. Sci. USA, 80: 1919.PubMedCrossRefGoogle Scholar
  19. Faggiotto, A. and Ross, R., 1984, Studies of hypercholesterolemia in the nonhuman primate. II. Fatty streak conversion to fibrous plaque. Arteriosclerosis, 4: 341.PubMedCrossRefGoogle Scholar
  20. Faggiotto, A., Ross, R. and Harker, L., 1984, Studies of hypercholesterolemia in the nonhuman primate. I. Changes that lead to fatty streak formation, Arteriosclerosis, 4: 323.PubMedCrossRefGoogle Scholar
  21. Feldman, D.L., Hoff, H.F. and Gerrity, R.G., 1984, Immunomicroscopic localization of Apo B in aortas from hyperlipemic swine. Preferential accumulation in lesion -prone areas, Arch. Pathol. Lab. Med., 108: 817.PubMedGoogle Scholar
  22. Gallin, J.I. and Kaplan, A.P., 1974, Mononuclear cell chemotactic activity of kallikrein and plasminogen activator and inhibition by CI inhibitor and 82-macroglobulin, J. Immunol., 129: 1612.Google Scholar
  23. Geer, J.C., McGill, H.C., Jr., and Strong, J.P., 1961, The fine structure of human atherosclerotic lesions, Am. J. Pathol., 38: 263.PubMedGoogle Scholar
  24. Gerrity, R.G., 1981a, The role of the monocyte in atherogenesis. I. Transition of blood-Google Scholar
  25. borne monocytes into foam cells in fatty lesions, Am. J. Pathol.,102:181. Gerrity, R.G., 1981 b, The role of the monocyte in atherogenesis. II. Migration of foamGoogle Scholar
  26. cells from atherosclerotic lesions, Am. J. Pathol.,103:191.Google Scholar
  27. Gerrity, R.G., Goss, J.A., and Soby, L., 1985, Control of monocyte recruitment by chemotactic factor(s) in lesion-prone areas of swine aorta, Arteriosclerosis, 5 (1): 55.PubMedCrossRefGoogle Scholar
  28. Gerrity, R.G., Richardson, M., Somer, J.B., Bell, F.P. and Schwartz, C.J., 1977, Endothelial cell morphology in areas of in vivo Evans blue uptake in the young pig aorta. II. Ultrastructure of the intima in areas of differing permeability of proteins, Am. J. Pathol., 89: 313.PubMedGoogle Scholar
  29. Gerrity, R.G., and Schwartz, C.J., 1977, Structural correlates of arterial endothelial permeability in the Evans blue model. in: “Progress in Biochemical Pharmacology”,H. Sinzinger, W. Auerswald, H. Jellinek, W. Feigl, eds., Karger, Switzerland. Vol 13: 134.Google Scholar
  30. Gerrity, R.G., Naito, H.K., Richardson, M., and Schwartz, C.J., 1979, Dietary-induced atherogenesis in swine. I. Morphology of the intima in pre-lesion stages, Am. J. Pathol., 95: 775.PubMedGoogle Scholar
  31. Hoff, H.F., Feldman, D.L. and Gerrity, R.G., 1983, Localization of LDL in arteries improvements in immunofluorescence procedures. In: “Defined Immunofluorescence and Related Cytochemical Methods”, E.H. Beutner, R.J. Nisencard and B.A. Albmi, eds., Ann. N.Y. Acad. Sci., Vol 420, p 159.Google Scholar
  32. Hoff, H.F., Gerrity, R.G., Naito, H.K. and Dusek, D.M., 1983, Quantitation of Apo B in aortas of hypercholesterolemic swine, Lab. Invest., 48: 492.PubMedGoogle Scholar
  33. Hoover, R.L., Folger, R., Haering, W.A., Ware, B.R. and Karnovsky, M.J., 1980, Adhesion of leukocytes to endothelium: Roles of divalent cations, surface charge, chemotactic agents and substrate, J. Cell Sci., 45: 73.PubMedGoogle Scholar
  34. Hunninghake, G.W., Davidson, J.M., Rennard, S., Szapiel, S., Gadek, J.R. and Crystal, R.G., 1981, Elastin fragments attract macrophage precursors to diseased sites in pulmonary emphysema, Science, 212: 925.PubMedCrossRefGoogle Scholar
  35. Jauchem, J.R., Lopez, M., Sprague, E.A. and Schwartz, C.J., 1982, Mononuclear cell chemoattractant activity from cultured arterial smooth muscle cells, Exp. Mol. Pathol., 37: 166.PubMedCrossRefGoogle Scholar
  36. 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.PubMedGoogle Scholar
  37. Jerome, W.G. and Lewis, J.C., 1985, Early atherogenesis in white carneau pigeons. II. Ultrastructural and cytochemical observations. Am. J. Pathol., 119: 210.PubMedGoogle Scholar
  38. Joris, I., Nunnari, T., Krolikowski, J.J. and Majno, F.J., 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.PubMedGoogle Scholar
  39. Kim, H.S., Suzuki, M. and O’Neal, R.M., 1966, The lipophage in hyperlipemic rats: An electron microscopic study, Exp. Mol. Pathol., 5: 1.CrossRefGoogle Scholar
  40. Leary, T., 1941, The genesis of atherosclerosis, Arch. Pathol., 32: 507.Google Scholar
  41. Leibovich, S.J. and Ross, R., 1976, A macrophage-dependent factor that stimulates the proliferation of fibroblasts in vitro, Am. J. Pathol., 84: 501.PubMedGoogle Scholar
  42. Macregor, R.R., Macarek, E.J. and Kefalides, N.A., 1978, Comparative adherence of granulocytes to endothelial monolayers and nylon fiber, J. Clin. Invest., 61:697.CrossRefGoogle Scholar
  43. Marshall, J.R. and O’Neal, R.M., 1966, The lipophage in hyperlipemic rats: An electron microscopic study. Exp. Mol. Pathol.,5:1.PubMedCrossRefGoogle Scholar
  44. McGill, H.C., Jr., 1968a, Persistent problems in the pathogenesis of atherosclerosis, Atherosclerosis, 4: 443.Google Scholar
  45. McGill, H.C., Jr., 1968b, “The Geographic Pathology of Atherosclerosis”,: Williams and Wilkins, Baltimore.Google Scholar
  46. Metcalf, D., 1977, Neutrophil and macrophage colony formation by normal cells, Recent Results in Canc. Res., 61: 56.Google Scholar
  47. Norris, D.A., Clark, R.A.F., Swigart, L.M., Huff, J.C., Weston, W.L. and Howell, S.E., 1982, Fibronectin fragment(s) are chemotactic for human peripheral blood monocytes, J. Immunol., 129: 1612.PubMedGoogle Scholar
  48. Poole, J.C.F. and Florey, H.W., 1958, Changes in the endothelium of the aorta and behaviour of macrophages in experimental atheroma of rabbits, J. Pathol. Bacteriol., 75: 245.PubMedCrossRefGoogle Scholar
  49. Robertson, W.B., Geer, J.C., Strong, J.P. and McGill, H.C., Jr., 1963, The fate of the fatty streak, Exp. Mol. Pathol. Suppl., 1: 38.Google Scholar
  50. Ross, R., 1986, The pathogenesis of atherosclerosis - An update, New England J. Med., 314: 488.CrossRefGoogle Scholar
  51. Ross, R., Wight, T.N., Strandness, E. and Thiele, B., 1984, Human atherosclerosis. I. Cell constitution and characteristics of advanced lesions of the superficial femoral artery, Am. J. Pathol., 11: 79.Google Scholar
  52. Somer, J.B., Gerrity, R.G. and Schwarts, C.J., 1976, Focal differences in lipid metabolism of the young pig aorta. III. Influence of insulin on lipogenesis form 14C-aAcetate, Exp. Mol. Path., 24: 1.CrossRefGoogle Scholar
  53. Somer, J.B. and Schwartz, C.J., 1976, Focal differences in lipid metabolism of the young pig aorta. IV. Influence of insulin and epinephrine of lipogenesis from 14C-Uglucose, Exp. Mol. Pathol., 24: 129.PubMedCrossRefGoogle Scholar
  54. Stary, H.C., 1985, Evolution and Progression of Atherosclerosis in the Coronary Arteries of Children and Adults. In: “Atherosclerosis and Aging”, S.R. Bates and E.C. Gaugloff, Springer-Verlag, Heidelberg, Berlin, New York, p 20.Google Scholar
  55. Still, W.J.S. and O’Neal, R.M., 1962, Electron Microscopic study of experimental atherosclerosis in the rat, Am. J. Pathol., 40: 21.PubMedGoogle Scholar
  56. Suzuki, M. and O’Neal, R.M., 1964, Accumulation of lipids in the leukocytes of rats fed atherogenic diets, J. Lipid Res., 5: 624.PubMedGoogle Scholar
  57. Suzuki, M. and O’Neal, R.M., 1967, Circulating lipophages, serum lipids and atherosclerosis in rats, Arch. Pathol., 83: 169.PubMedGoogle Scholar
  58. Synderman, R. and Friedman, E.J., 1980, Demonstration of a chemotactic factor receptor on macrophages, J. Immunol., 124: 2754.Google Scholar
  59. Synderman, R., Shin, H.S. and Hausman, M.S., 1971, A chemotactic factor for mononuclear leukocytes, Proc. Soc. Exp. Biol. Med., 138: 387.Google Scholar
  60. Wissler, R.W. and Vesselinovitch, D., 1977, Atherosclerosis in nonhuman primates, Adv. Vet. Sci. Comp. Med., 21: 351.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Ross G. Gerrity
    • 1
  • Lynn E. Averill
    • 1
  1. 1.Cardiovascular Research Center Cleveland Research InstituteSt. Vincent Charity Hospital and Health CenterClevelandUSA

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