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. 1981 May;103(2):191–200.

The role of the monocyte in atherogenesis: II. Migration of foam cells from atherosclerotic lesions.

R G Gerrity
PMCID: PMC1903828  PMID: 7234962

Abstract

A defined role in the atherogenic sequence is proposed for the circulating monocyte. The author has been able to demonstrate a "monocyte clearance system" in which large numbers of circulating monocytes invade the intima of lesion-prone areas in arteries, become phagocytic, and accumulate lipid. A fatty cell lesion results. Once lipid-laden, foam cells migrate back into the bloodstream by crossing the arterial endothelium. The ratio of penetrating monocytes to emerging foam cells decreases as fatty cell lesions develop until a one-to-one ratio is achieved in late fatty cell lesions, which do not progress further. Advanced fibroatherosclerotic plaques in the same animals do not show the same characteristics and have smooth muscle cell involvement. It would appear that advancement of the lesion is at least partially a result of failure of the monocyte clearance system to remove sufficient lipid. The invasion of monocytes and endothelial damage caused by foam cell clearance may, in late fatty lesions, contribute to plaque evolution by introducing growth factors from macrophages and platelets and allowing greater lipid influx. Elucidation of this system was facilitated by the examination of vessels from diet initiation onwards and by the observation of late nonprogressing fatty cell lesions. It is possible that this system exists in other models but has been overlooked by a predilection for the study of advanced lesions that prevails in the literature.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adams C. W., Bayliss O. B. Detection of macrophages in atherosclerotic lesions with cytochrome oxidase. Br J Exp Pathol. 1976 Feb;57(1):30–36. [PMC free article] [PubMed] [Google Scholar]
  2. Adams C. W., Bayliss O. B., Turner D. R. Phagocytes, lipid-removal and regression of atheroma. J Pathol. 1975 Aug;116(4):225–238. doi: 10.1002/path.1711160406. [DOI] [PubMed] [Google Scholar]
  3. Fischer-Dzoga K., Fraser R., Wissler R. W. Stimulation of proliferation in stationary primary cultures of monkey and rabbit aortic smooth muscle cells. I. Effects of lipoprotein fractions of hyperlipemic serum and lymph. Exp Mol Pathol. 1976 Jun;24(3):346–359. doi: 10.1016/0014-4800(76)90070-8. [DOI] [PubMed] [Google Scholar]
  4. GEER J. C., McGILL H. C., Jr, STRONG J. P. The fine structure of human atherosclerotic lesions. Am J Pathol. 1961 Mar;38:263–287. [PMC free article] [PubMed] [Google Scholar]
  5. Gaton E., Wolman M. The role of smooth muscle cells and hematogenous macrophages in atheroma. J Pathol. 1977 Oct;123(2):123–128. doi: 10.1002/path.1711230208. [DOI] [PubMed] [Google Scholar]
  6. Geer J. C. Fine structure of human aortic intimal thickening and fatty streaks. Lab Invest. 1965 Oct;14(10):1764–1783. [PubMed] [Google Scholar]
  7. Gerrity R. G., Naito H. K., Richardson M., Schwartz C. J. Dietary induced atherogenesis in swine. Morphology of the intima in prelesion stages. Am J Pathol. 1979 Jun;95(3):775–792. [PMC free article] [PubMed] [Google Scholar]
  8. Gerrity R. G., Richardson M., Somer J. B., Bell F. P., Schwartz C. J. Endothelial cell morphology in areas of in vivo Evans blue uptake in the aorta of young pigs. II. Ultrastructure of the intima in areas of differing permeability to proteins. Am J Pathol. 1977 Nov;89(2):313–334. [PMC free article] [PubMed] [Google Scholar]
  9. Grant R. A. Content and distribution of aortic collagen, elastin and carbohydrate in different species. J Atheroscler Res. 1967 Jul-Aug;7(4):463–472. doi: 10.1016/s0368-1319(67)80024-3. [DOI] [PubMed] [Google Scholar]
  10. Jones R. M., Schaffner T. J., Chassagne G., Glagov S., Wissler R. W. Comparison of coronary with aortic fatty streaks in rhesus monkeys. Scan Electron Microsc. 1979;(3):829–834. [PubMed] [Google Scholar]
  11. Kim H. S., Suzuki M., O'Neal R. M. Leukocyte lipids of human blood. Am J Clin Pathol. 1967 Sep;48(3):314–319. doi: 10.1093/ajcp/48.3.314. [DOI] [PubMed] [Google Scholar]
  12. Leibovich S. J., Ross R. A macrophage-dependent factor that stimulates the proliferation of fibroblasts in vitro. Am J Pathol. 1976 Sep;84(3):501–514. [PMC free article] [PubMed] [Google Scholar]
  13. Marshall J. R., O'Neal R. M. The lipophage in hyperlipemic rats: an electron microscopic study. Exp Mol Pathol. 1966 Feb;5(1):1–11. doi: 10.1016/0014-4800(66)90002-5. [DOI] [PubMed] [Google Scholar]
  14. Ross R., Glomset J. A. Atherosclerosis and the arterial smooth muscle cell: Proliferation of smooth muscle is a key event in the genesis of the lesions of atherosclerosis. Science. 1973 Jun 29;180(4093):1332–1339. doi: 10.1126/science.180.4093.1332. [DOI] [PubMed] [Google Scholar]
  15. Ross R., Glomset J. A. The pathogenesis of atherosclerosis (second of two parts). N Engl J Med. 1976 Aug 19;295(8):420–425. doi: 10.1056/NEJM197608192950805. [DOI] [PubMed] [Google Scholar]
  16. Ross R., Vogel A. The platelet-derived growth factor. Cell. 1978 Jun;14(2):203–210. doi: 10.1016/0092-8674(78)90107-1. [DOI] [PubMed] [Google Scholar]
  17. STILL W. J., O'NEAL R. M. Electron microscopic study of experimental atherosclerosis in the rat. Am J Pathol. 1962 Jan;40:21–35. [PMC free article] [PubMed] [Google Scholar]
  18. SUZUKI M., O'NEAL R. M. ACCUMULATION OF LIPIDS IN THE LEUKOCYTES OF RATS FED ATHEROGENIC DIETS. J Lipid Res. 1964 Oct;5:624–627. [PubMed] [Google Scholar]
  19. Schaffner T., Taylor K., Bartucci E. J., Fischer-Dzoga K., Beeson J. H., Glagov S., Wissler R. W. Arterial foam cells with distinctive immunomorphologic and histochemical features of macrophages. Am J Pathol. 1980 Jul;100(1):57–80. [PMC free article] [PubMed] [Google Scholar]
  20. Stary H. C. Coronary artery fine structure in rhesus monkeys: the early atherosclerotic lesion and its progression. Primates Med. 1976;9:359–395. [PubMed] [Google Scholar]
  21. Stary H. C., Strong J. P. The fine structure of nonatherosclerotic intimal thickening, of developing, and of regressing atherosclerotic lesions at the bifurcation of the left coronary artery. Adv Exp Med Biol. 1976;67(00):89–108. doi: 10.1007/978-1-4614-4618-7_5. [DOI] [PubMed] [Google Scholar]
  22. Stefanovich V., Gore I. Cholesterol diet nd permeability of rabbit aorta. Exp Mol Pathol. 1971 Feb;14(1):20–29. doi: 10.1016/0014-4800(71)90049-9. [DOI] [PubMed] [Google Scholar]
  23. Suzuki M., O'Neal R. M. Circulating lipophages, serum lipids, and atherosclerosis in rats. Arch Pathol. 1967 Feb;83(2):169–174. [PubMed] [Google Scholar]
  24. Taylor K., Schaffner T., Wissler R. W., Glagov S. Immuno-morphologic identification and characterization of cells derived from experimental atherosclerotic lesions. Scan Electron Microsc. 1979;(3):815–822. [PubMed] [Google Scholar]
  25. Weber G., Fabbrini P., Capaccioli E., Resi L. Repair of early cholesterol-induced aortic lesions in rabbits after withdrawal from short-term atherogenic diet. Scanning electron-microscopical (SEM) and transmission electron-microscopical (TEM) observations. Atherosclerosis. 1975 Nov-Dec;22(3):565–572. doi: 10.1016/0021-9150(75)90034-9. [DOI] [PubMed] [Google Scholar]

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