Pathobiology of Atherosclerosis

  • Assaad S. Daoud
  • Katherine E. Fritz
  • John Jarmolych
  • Mark L. Armstrong


The normal arterial wall is an ordered structure in which the principal cellular components, smooth muscle cells, and endothelial cells, are arranged in a predictable relationship to each other and to the extracellular substances, most of which are collagen, elastin, and glycosaminoglycans. The development of an atherosclerotic lesion disturbs normal spatial relationships by altering both the cellular and extracellular composition. The cellular changes involve most notably an increase in smooth muscle cells (SMC) and the appearance of numerous “foam cells,” lipid-filled cells of unidentifiable origin, as well as macrophages (1). Also documented are increases in such extracellular substances as total and esterified cholesterol, phospholipid, elastin (2) and calcium (3). These changes are accompanied by areas of necrosis (1). During the regression process the numbers of foam cells and macrophages decrease (1,4), as does lipid concentration (5–7), including total and esterified cholesterol (3,7–9). Depending on the regression regimen employed, calcium concentration may decrease (5,6,8) or increase (3), while collagen concentration has similarly been reported to increase (8) or decrease (9). A decrease in the amount of necrosis is a relatively early phenomenon (1).


Smooth Muscle Cell Foam Cell Aortic Smooth Muscle Cell Bovine Aortic Endothelial Cell Arterial Smooth Muscle Cell 
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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  1. 1.
    Daoud AS, Jarmolych J, Augustyn JM, Fritz KE (1981) Sequential morphologic studies of regression of advanced atherosclerosis. Arch Path Lab Med 105: 233–239PubMedGoogle Scholar
  2. 2.
    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: 360–385PubMedCrossRefGoogle Scholar
  3. 3.
    Fritz KE, Augustyn JM, Jarmolych J, Daoud AS (1981) Sequential study of biochemical changes during regression of swine aortic atherosclerotic lesions. Arch Path Lab Med 105: 240–246PubMedGoogle Scholar
  4. 4.
    Stary HC (1979) Regression of atherosclerosis in primates. Virchows Arch LPathol Anat 383: 117–134Google Scholar
  5. 5.
    Wagner WD, Clarkson TB, Foster J (1977) Contrasting effects of ethane-l-hydroxy-1, 1-diphosphonate ( EHDP) on the regression of two types of dietary-induced atherosclerosis. Atherosclerosis 27: 419–435PubMedCrossRefGoogle Scholar
  6. 6.
    Hollander W, Paddock J, Nagraj S, Colombo M, Kirkpatrick B (1979) Effects of anticalcifying and antifrobrotic drugs on pre-established atherosclerosis in the rabbit. Atherosclerosis 33: 111–123PubMedCrossRefGoogle Scholar
  7. 7.
    Armstrong ML, Megan MB (1972) Lipid depletion in atheromatous coronary arteries in rhesus monkeys after regression diets. Circ Res 30: 675–680PubMedGoogle Scholar
  8. 8.
    Wagner WD, St Clair RW, Clarkson TB (1980) A study of atherosclerosis regression in Macaca mulatta: II. Chemical changes in arteries from animals with atherosclerosis induced for 19 months then regressed for 24 months at plasma cholesterol concentration of 300 or 200 mg/dl. Exp Mol Pathol 32: 162–174PubMedCrossRefGoogle Scholar
  9. 9.
    Wissler RW, Vesselinovitch D (1977) Regression of atherosclerosis in experimental animals and man. Mod Concepts Cardiovasc Dis 46: 27–32PubMedGoogle Scholar
  10. 10.
    Ross R (1981) Atherosclerosis: a problem of the biology of arterial wall cells and their interactions with blood components. Arteriosclerosis 1: 293–311PubMedCrossRefGoogle Scholar
  11. 11.
    Wissler RW (1980) Principles of the pathogenesis of atherosclerosis. In: Braunwall E (ed) Heart disease: a textbook of cardiovascular medicine. WB Sanders Co, Philadelphia, pp 1221–1245Google Scholar
  12. 12.
    Schwartz SM, Gajdusek CM, Selden SC III (1981) Vascular wall growth control: the role of the endothelium. Arteriosclerosis 1: 107–126PubMedCrossRefGoogle Scholar
  13. 13.
    Ives HE, Schultz GS, Galardy RE, Jamieson JD (1978) Preparation of functional smooth muscle cells from the rabbit aorta. J Exp Med 148: 1400–1413PubMedCrossRefGoogle Scholar
  14. 14.
    Chamley-Campbell JH, Campbell GR, Ross R (1981) Phenotype-dependent response of cultural aortic smooth muscle cells to serum mitogens. J Cell Biol 89: 379–383PubMedCrossRefGoogle Scholar
  15. 15.
    Daoud AS, Fritz KE, Jarmolych J, Augustyn JM (1973) Use of aortic medial explants in the study of atherosclerosis. Exp Mol Pathol 18: 177–189PubMedCrossRefGoogle Scholar
  16. 16.
    Fischer-Dzoga K, Wissler RW (1976) Stimulation of proliferation in stationary primary cultures of monkey aortic smooth muscle cells. Part 2. Effect of varying concentrations of hyperlipemic serum and low density lipoproteins of varying dietary fat origins. Atherosclerosis 24: 515–525PubMedCrossRefGoogle Scholar
  17. 17.
    Brennen MJ, Fritz KE, Millis AJT (1980) Density-dependent nodulation of smooth muscle cell cultures. J Cell Biol 87: 59a (abstract)Google Scholar
  18. 18.
    Gimbrone MK, Cotran RL (1975) Human vascular smooth muscle in culture. Lab Invest 33: 16–27PubMedGoogle Scholar
  19. 19.
    Gottlieb AI, Spector W (1981) Migration into an in vitro experimental wound. A comparison of porcine aortic endothelial and smooth muscle cells and the effect of culture irradiation. Am J Pathol 103: 271–282Google Scholar
  20. 20.
    Thorgeirsson G, Robertson AL Jr, Cowan DH (1979) Migration of human vascular endothelial and smooth muscle cells. Lab Invest 41: 51–62PubMedGoogle Scholar
  21. 21.
    Daoud AS, Fritz KE, Jarmolych J, Augustyn JM, Mawhinney TM (1977) Production of glycosaminoglycans, collagen and elastic tissue by aortic medial explants. In: Manning GW, Haust MD (eds) Atherosclerosis, metabolic and clinical aspects. Plenum Publishing Corp, New York, pp 928–933Google Scholar
  22. 22.
    Wight TN, Ross R (1975) Proteoglycans in primate arteries. II. Synthesis and secretion of glycosaminoglycans by arterial smooth muscle cells in culture. J Cell Biol 67: 675–686PubMedCrossRefGoogle Scholar
  23. 23.
    Wight TN (1980) Differences in the synthesis and secretion of sulfated glycosaminoglycans by aorta explant monolayers cultured from atherosclerosis-susceptible and resistant pigeons. Am J Pathol 101: 127–142PubMedGoogle Scholar
  24. 24.
    Larjava H, Saarni H, Tammi M, Penttinen R, Ronnemaa T (1980) Cortisol decreases the synthesis of hyaluronic acid by human aortic smooth muscle cells in culture. Atherosclerosis 35: 135–143PubMedCrossRefGoogle Scholar
  25. 25.
    McCullagh KA, Balian G (1975) Collagen characterization and cell transformation in human atherosclerosis. Nature 258: 73–75PubMedCrossRefGoogle Scholar
  26. 26.
    Fritz KE, Daoud AS, Jarmolych J (1981) Cholesteryl ester hydrolase and S-glucuronidase activities in swine aortic lesions. Fed Proc 40: 351Google Scholar
  27. 27.
    Fritz KE, Daoud AS, Jarmolych J (to be published) Collagenolytic activity in swine aortic atherosclerotic lesions. Fed Proc (abstract)Google Scholar
  28. 28.
    Hayes LW, Goguen CA, Stevens AL, Magargal WW, Slakey LL (1979) Enzyme activities in endothelial cells and smooth muscle cells from swine aorta. Proc Natl Acad Sci USA 76: 2532–2535PubMedCrossRefGoogle Scholar
  29. 29.
    Kerwar SS, Nolan JC, Ridge SC, Oronsky AL, Slakey T.L. (1980) Properties of a collagenase inhibitor partially purified from cultures of smooth muscle cells. Biochim Biophys Acta 632: 183–191PubMedCrossRefGoogle Scholar
  30. 30.
    Goldstein JL, Brown NS (1977) The low density lipoprotein pathway and its relation to atherosclerosis. Annu Rev Biochem 46: 897–930PubMedCrossRefGoogle Scholar
  31. 31.
    Karnovsky MJ (1981) Endothelial-vascular smooth muscle cell interactions. Am J Pathol 105: 200–206 (Rous-Whipple Award Lecture)Google Scholar
  32. 32.
    Bierman EL, Albers J (1977) Regulation of low density lipoprotein receptor activity by cultured human arterial smooth muscle cells. Biochim Biophys Acta 488: 152–160PubMedGoogle Scholar
  33. 33.
    Davies PF, Ross R (1978) Mediation of pinocytosis in cultured arterial smooth muscle and endothelial cells by platelet-derived growth factor. J Cell Biol 79: 663–671PubMedCrossRefGoogle Scholar
  34. 34.
    Simpson CF (1977) Phagocytosis by aortic modified smooth muscle cells. Artery 3: 210–217Google Scholar
  35. 35.
    Garfield RE, Chacka S, Blose S (1975) Phagocytosis by muscle cells. Lab Invest 33: 418–427PubMedGoogle Scholar
  36. 36.
    Thomas WA, Florentin RA, Nam SC, Jones RM, Lee KT (1968) Preproliferative phase of atherosclerosis in swine fed cholesterol. Arch Path Lab Med 86: 621–643Google Scholar
  37. 37.
    Huttner I, Boutet M, More RH (1973) Studies on protein passage through arterial endothelium. Lab Invest 28: 672–677PubMedGoogle Scholar
  38. 38.
    Simionescu N, Simionescu M, Palade GE (1975) Permeability of muscle capillaries to small hemepeptides. Evidence for the existence of patent transendothelial channels. J Cell Biol 64: 586–607PubMedCrossRefGoogle Scholar
  39. 39.
    Sholley MM, Gimbrone MA, Cotran RS (1977) Cellular migration and replication in endothelial regeneration. A study using irradiated endothelial cultures. Lab Invest 36: 18–25PubMedGoogle Scholar
  40. 40.
    Gold LI, Pearlstein E (1980) Fibronectin-collagen binding and requirement during cellular adhesion. Biochem J 186: 551–559PubMedGoogle Scholar
  41. 41.
    Gajdusek CM, DiCorleto P, Ross R, Schwartz SM (1980) An endothelial-cell-derived growth factor. J Cell Biol 85: 467–472PubMedCrossRefGoogle Scholar
  42. 42.
    Castellot JJ Jr, Addonizio ML, Rosenberg R, Karnovsky MJ (1981) Cultured endothelial cells produce a heparin-like inhibitor of smooth muscle cell growth. J Cell Biol 90: 372–379PubMedCrossRefGoogle Scholar
  43. 43.
    Cotta-Pereira G, Sage H, Bornstein P, Ross R, Schwartz SM (1980) Studies of morphologically atypical (“Sprouting”) cultures of bovine aortic endothelial cells. Growth characteristics and connecting tissue protein synthesis. J Cell Physiol 102: 183–191PubMedCrossRefGoogle Scholar
  44. 44.
    Sage H, Crouch E, Bornstein P (1979) Collagen synthesis by bovine aortic endothelial cells in culture. Biochemistry 18: 5433–5442PubMedCrossRefGoogle Scholar
  45. 45.
    Sage H, Pritzl P, Bornstein P (1981) Characterization of cell matrix associated collagens synthesized by aortic endothelial cells in culture. Biochemistry 20: 436–442PubMedCrossRefGoogle Scholar
  46. 46.
    Jaffe EA, Minick CR, Adelman B, Becker CG, Nachman R (1976) Synthesis of basement membrane collagen by cultured human endothelial cells. J Exp Med 144: 209–225PubMedCrossRefGoogle Scholar
  47. 47.
    Saba TM, Jaffe EA (1980) Plasma fibronectin (opsonic glycoprotein): Its synthesis by vascular endothelial cells and role in cardio-pulmonary integrity after trauma as related to reticuloendothelial function. Am J Med 68: 577–594PubMedCrossRefGoogle Scholar
  48. 48.
    Jaffe EA, Hoyer LW, Nachman RL (1973) Synthesis of anti-hemophilic factor antigen by cultured human endothelial cells. J Clin Invest 52: 2757–2764PubMedCrossRefGoogle Scholar
  49. 49.
    Jaffe EA, Weksler BR (1979) Recovery of endothelial cell prostacylin production after inhibition and low doses of aspirin. J Clin Invest 63: 532–535PubMedCrossRefGoogle Scholar
  50. 50.
    Ryan US, Schultz DR, Ryan JW (1981) Fc and C3b receptors on pulmonary endothelial cells: induction by injury. Science 214: 557–558PubMedCrossRefGoogle Scholar
  51. 51.
    Vlodaysky I, Fielding PE, Fielding CJ, Gospodarowicz D (1978) Role of contact inhibition in the regulation of receptor-mediated uptake of low density lipoprotein in cultured vascular endothelial cells. Proc Natl Acad Sci 75: 356–360CrossRefGoogle Scholar
  52. 52.
    Fielding CJ, Vlodaysky I, Fielding PE, Gospodarowicz D (1979) Characteristics of chylomicron binding and lipid uptake by endothelial cells in culture. J Biol Chem 254: 8861–8868PubMedGoogle Scholar
  53. 53.
    Gospodarowicz D, Brown KD, Birdwell CR, Zetter BR (1978) Control of proliferation of human vascular endothelial cells. Characterization of the response of human umbilical vein endothelial cells to fibroblast growth factor, epidermal growth factor and thrombin. J Cell Biol 77: 774–788PubMedCrossRefGoogle Scholar
  54. 54.
    Busch C, Dawes DS, Wasteson P, Wasteson A. (1979) Binding of platelet factor N to cultured endothelial cells. Thromb Haemost 42: 43Google Scholar
  55. 55.
    Hope W, Martin TJ, Chesterman CN, Morgan FJ (1979) Human (3-thromboglobulin inhibits PGI2 production and binds to a special site in bovine aortic endothelial cells. Nature 282: 210–212PubMedCrossRefGoogle Scholar
  56. 56.
    Hoover RL, Folger R, Haering WA, Ware BR, Karnovsky MJ (1980) Adhesion of leukocytes to endothelium: roles of divalent cations, surface charge, chemotactic agents and substrate. J. Cell Sci 45: 73–86PubMedGoogle Scholar
  57. 57.
    Hollander W, Columbo MA, Kramsch DM, Kirkpatrick B (1974) Immunological aspects of atherosclerosis. Adv Cardiol 13: 192–207PubMedGoogle Scholar
  58. 58.
    Lamberson HV Jr, Fritz KE (1974) Immunological enhancement of atherogenesis in rabbits. Arch Pathol 98: 9–16PubMedGoogle Scholar
  59. 59.
    Hardin NJ, Minick R, Murphy GE (1973) Experimental induction of athero-arteriosclerosis by the synergy of allergic injury to arteries and lipid-rich diet. Am J Pathol 73: 301–325PubMedGoogle Scholar
  60. 60.
    Gerrity RG (1981) The role of monocyte in atherogenesis: I. Transition of blood borne monocytes into foam cells in fatty lesions. Am J Pathol 103: 181–190PubMedGoogle Scholar
  61. 61.
    Gerrity RG (1981) The role of monocyte in atherogenesis: II. Migration of foam cells from atherosclerotic lesions. Am J Pathol 103: 191–200PubMedGoogle Scholar
  62. 62.
    Issekutz TB, Issekutz AC, Movat HC (1981) The in vivo quantitation and kinetics of monocyte migration into acute inflammatory tissue. Am J Pathol 103: 47–55PubMedGoogle Scholar
  63. 63.
    Steinman RM, Cohn ZA (1974) The metabolism and physiology of the mononuclear phagocytes. In: Zweifach BW, Grant L, McClusky RT (eds) The inflammatory process. Academic Press, New York, San Francisco, London, pp 449–510Google Scholar
  64. 64.
    Schaffner T, Taylor K, Bartucci EJ, Fisher-Dzoga K, Beeson JH, Glagov S, Wissler RW (1980) Arterial foam cells with distinctive immunomorphologic and histochemical features of macrophages. Am J Pathol 100: 57–80PubMedGoogle Scholar
  65. 65.
    Fritz KE, Daoud AS, Jarmolych J. Unpublished data.Google Scholar
  66. 66.
    Rifkin BR, Baker RL, Somerman MJ, Pointon SE, Coleman SJ, Au WYW (1980) Osteoid resorption by mononuclear cells in vitro. Cell Tissue Res 210: 493–500PubMedCrossRefGoogle Scholar
  67. 67.
    Cohn ZA (1978) The activation of mononuclear phagocytes; fact, fancy and future. J Immunol 121: 813–816PubMedGoogle Scholar
  68. 68.
    Kulonen E, Potila M (1980) Macrophages and the synthesis of connective tissue components. Acta Path Microbiol Scand (C) 88: 7–13Google Scholar
  69. 69.
    Werb Z, Banda MJ, Jones PA (1980) Degradation of connective tissue matrices by macrophages. I. Proteolysis of elastin, glycoproteins and collagen by proteinases isolated from macrophage. J Exp Med 152: 1340–1357PubMedCrossRefGoogle Scholar
  70. 70.
    Werb Z, Gordon S (1975) Elastase secretion by stimulated macrophages. Characterization and regulation. J Exp Med 142: 361–377PubMedCrossRefGoogle Scholar
  71. 71.
    Werb Z, Gordon S (1975) Secretion of a specific collagenase by stimulated macrophages. J Exp Med 142: 346–360PubMedCrossRefGoogle Scholar
  72. 72.
    Unane ER (1976) Secretory function of mononuclear phagocytes. Am J Pathol 83: 396–417Google Scholar
  73. 73.
    Cohn ZA, Wiener E (1963) The particulate hydrolases of macrophages. I. Comparative enzymology, isolation and properties. J Exp Med 118: 991–1008PubMedCrossRefGoogle Scholar
  74. 74.
    Unkeless JC, Gordon S, Reich E (1974) Secretion of plasminogen activator by stimulated macrophages. J Exp Med 139: 834–850PubMedCrossRefGoogle Scholar
  75. 75.
    Martin BM, Gimbrone MA Jr, Unanue ER, Cotran RS (1981) Stimulation of nonlymphoid mesenchymal cell proliferation by a macrophage-derived growth factor. J Immunol 126: 1510–1515PubMedGoogle Scholar
  76. 76.
    Glenn KC, Ross R (1981) Human monocyte-derived growth factor(s) for mesenchymal cells: activation of secretion by endotoxin and concanavalin A ( CON A ). Cell 25: 603–615PubMedCrossRefGoogle Scholar
  77. 77.
    Villiger B, Kelley DG, Engleman W, Kuhn C III, McDonald JA (1981) Human alveolar macrophage fibronectin: synthesis, secretion and ultrastructural localization during gelatin-coated latex particle binding. J Cell Biol 90: 711–720PubMedCrossRefGoogle Scholar
  78. 78.
    Alitalo K, Hovi T, Vaheri A (1980) Fibronectin is produced by human macrophages. J Exp Med 151: 602–613PubMedCrossRefGoogle Scholar
  79. 79.
    Johansson S, Rubin K, Hook M, Ahlgren T, Seljelid R (1979) In Vitro biosynthesis of cold insoluble globulin (fibronectin) by mouse peritoneal macrophages. FEBS Letters 105: 213–216CrossRefGoogle Scholar
  80. 80.
    Schechter I, Fogelman AM, Haberland ME, Seager J, Hokom M, Edwards PA (1981) The metabolism of native and malondialdehyde altered low-density lipoproteins by human monocyte-macrophages. J Lipid Res 22: 863–871Google Scholar
  81. 81.
    Merrilees MJ, Scott L (1981) Interaction of aortic endothelial and smooth muscle cells in culture. Effect on glycosaminoglycan levels. Atherosclerosis 39: 147–161PubMedCrossRefGoogle Scholar
  82. 82.
    Olivecrona T, Bengtsson G, Marklund SE, Lindahl U, Hook M (1977) Heparin-lipoprotein lipase interactions. Fed Proc 36: 60–65PubMedGoogle Scholar
  83. 83.
    Clowes AW, Karnovsky MJ (1977) Suppression by heparin of smooth muscle cell proliferation in injured arteries. Nature 265: 625–626PubMedCrossRefGoogle Scholar
  84. 84.
    Traber MG, Kayden HJ (1980) Low density lipoprotein receptor activity in human monocyte-derived macrophages and its relation to atheromatous lesions. Proc Natl Acad Sci 77: 5466–5470PubMedCrossRefGoogle Scholar
  85. 85.
    Fischer-Dzoga K (1979) Cellular proliferation, cellular death and atherosclerosis. Artery 5: 222–236PubMedGoogle Scholar
  86. 86.
    Feo F, Canuto RA, Torrielli MV, Garcea R, Dianzani MU (1976) Effect of a cholesterol-rich diet on cholesterol content and phagocytic activity of rat macrophages. Agents and Actions 6: 135–142PubMedCrossRefGoogle Scholar
  87. 87.
    Klurfeld DM, Allison MJ, Gerszten E, Dalton HP (1979) Alterations of host defenses paralleling cholesterol-induced atherogenesis. II. Immunologic studies of rabbits. J Med 10: 49–64PubMedGoogle Scholar
  88. 88.
    Mahley RW, Innerarity TL, Brown MS, Ho YK, Goldstein JL (1980) Cholesteryl ester synthesis in macrophages: stimulation by P,-very low density lipoproteins from cholesterol-fed animals of several species. J Lipid Res 21: 970–980PubMedGoogle Scholar
  89. 89.
    Jackson RL, Stein O, Gotto AN, Stein Y (1975) A comparative study on the removal of cellular lipids from Lundschutz ascites cells by human plasma apolipoproteins. J Biol Chem 250: 7204–7209PubMedGoogle Scholar
  90. 90.
    Wight TN (1980) Vessel proteoglycans and thrombogenesis. In: Spaet H (ed) Progress in hemostasis and thrombosis, 5th edn. Greene and Stratton, New York, 1980, pp 1–39Google Scholar
  91. 91.
    Van de Water L III, Schroeder S, Crenshaw EB III, Hynes RO (1981) Phagocytosis of gelatin-latex particles by a murine macrophage line is dependent on fibronectin and heparin. J Cell Biol 90: 32–39PubMedCrossRefGoogle Scholar
  92. 92.
    Love SH, Shannon BT, Myrvik QN, Lynn WS (1979) Characterization of macrophage agglutinating factor as a hyaluronic acid-protein complex. J Reticuloendothel Soc 25: 269–282PubMedGoogle Scholar
  93. 93.
    Jones PA, Werb Z (1980) Degradation of connective tissue matrices by macrophages. II. Influence of matrix composition on proteolysis of glycoproteins, elastin, and collagen by macrophages in culture. J Exp Med 152: 1527–1536Google Scholar
  94. 94.
    Berenson GS, Radhakrishnamurthy B, Dalferes ER Jr, Srinwasan SR (1971) Carbohydrate macromolecules and atherosclerosis. Hum Pathol 2: 57–79PubMedCrossRefGoogle Scholar
  95. 95.
    Stevens RL, Colombo M, Gonzales JJ, Hollander W, Schmid K (1976) The glycosaminoglycans of the human artery and their changes in atherosclerosis. J Clin Invest 58: 470–481PubMedCrossRefGoogle Scholar
  96. 96.
    Avila EM, Lopez F, Camejo G (1978) Properties of low density lipoprotein related to its interaction with arterial wall components: in vitro and in vivo studies. Artery 4: 36–60Google Scholar
  97. 97.
    Biheri-Varga M, (1978) Influence of serum high density lipoproteins on the low density lipoprotein-aortic glycosaminoglycan interactions. Artery 4: 504–511Google Scholar
  98. 98.
    Iverius PH (1977) Possible role of glycosaminoglycans in the genesis of atherosclerosis. In: Atherogenesis initiating factors. Ciba Symposium 12. Elsevier, North Holland, Amsterdam 7: 185–196Google Scholar
  99. 99.
    Radhakrishnamurthy B, Ruiz HA Jr, Berenson GS (1977) Isolation and characterization of proteoglycans from bovine aorta. J Biol Chem 252: 4831–4841PubMedGoogle Scholar
  100. 100.
    Klynstra FB, Böttcher CJF, Van Melsen JA, Van der Laan EJ (1967) Distribution and composition of acid mucopolysaccharides in normal and atherosclerotic human aortas. J Atheroscler Res 7: 301–309PubMedCrossRefGoogle Scholar
  101. 101.
    Yamada KM, Kennedy DW, Kimata K, Pratt RM (1980) Characteristics of fibronectin interactions with glycosaminoglycans and identification of active proteolytic fragments. J Biol Chem 255: 6055–6063PubMedGoogle Scholar
  102. 102.
    Kramsch DM, Franzblau C, Hollander W (1971) The protein and lipid composition of arterial elastin and its relationship to lipid accumulation in the atherosclerotic plaque. J Clin Invest 50: 1666–1677PubMedCrossRefGoogle Scholar
  103. 103.
    Keeley FW, Partridge SM (1974) Aminoacid composition and calcification of human aortic elastin. Atherosclerosis 19: 287–296PubMedCrossRefGoogle Scholar
  104. 104.
    Modrak JB, Langner RO (1980) Possible relationship of cholesterol accumulation and collagen synthesis in rabbit aortic tissues. Atherosclerosis 37: 211–218PubMedCrossRefGoogle Scholar
  105. 105.
    Kramsch DM, Chan CT, Aspen AJ, Wells H (1978) Prevention therapy of induced atherosclerosis in rabbits and monkeys regardless of serum cholesterol levels. In: Haust WH, Wissler RW, Lehman R (eds) International symposium: state of prevention and therapy in human arteriosclerosis and in animal models. Westdeutscher Verlag, Oppladen, pp 153–172Google Scholar
  106. 106.
    Perlin AS (1977) NMR spectroscopy of heparin. Fed Proc 36: 106–109PubMedGoogle Scholar
  107. 107.
    Stivala SS (1977) Physicochemical properties of heparin and its interaction with Cu (II) and calcium in relation to acticoagulation. Fed Proc 36: 83–88PubMedGoogle Scholar
  108. 108.
    Engelberg H (1977) Probably physiologic functions of heparin. Fed Proc 36: 70–72PubMedGoogle Scholar
  109. 109.
    Stemerman MB (1975) Vascular intimai components: precursors of thrombosis. In: Spaet TH (ed) Hemostasis and thrombosis. Grune and Stratton Inc, New York, pp 1–47Google Scholar
  110. 110.
    Daoud AS, Jarmolych J, Augustyn JM, Fritz KE, Singh JK, Lee KT (1976) Regression of advanced atherosclerosis in swine. Arch Pathol Lab Med 100: 372–379PubMedGoogle Scholar
  111. 111.
    Ennever J, Vogel JJ, Levy BM (1974) Lipid and bone matrix calcification in vitro. Proc Soc Exp Biol Med 145: 1386–1388PubMedGoogle Scholar
  112. 112.
    Ennever J, Vogel JJ, Riggan LJ, Paoloski SB (1977) Proteo-lipid and calculus matrix calcification in vitro. J Dent Res 56: 140–142PubMedCrossRefGoogle Scholar
  113. 113.
    Ennever J, Vogel JJ, Rider LJ, Boyan-Salyers B (1976) Nucleation of microbiologic calcification by proteolipid. Proc Soc Exp Biol Med 152: 147–150PubMedGoogle Scholar
  114. 114.
    Ennever J, Vogel JJ, Riggan LJ (1980) Calcification by proteolipid from atherosclerotic aorta. Atherosclerosis 35: 209–213PubMedCrossRefGoogle Scholar
  115. 115.
    Schmid K, McSharry WO, Pameijer CH, Binette JP (1980) Chemical and physicochemical studies on the mineral deposits of the human atherosclerotic aorta. Atherosclerosis 37: 199–210PubMedCrossRefGoogle Scholar
  116. 116.
    Kim KM (1976) Calcification of matrix vesicles in human aortic valve and aortic media. Fed Proc 35: 156–162PubMedGoogle Scholar
  117. 117.
    Martin GR, Schiffmann E, Bladen HA, Nylen M (1963) Chemical and morphological studies of the in vitro calcification of aorta. J Cell Biol 16: 243–252PubMedCrossRefGoogle Scholar
  118. 118.
    Andersson R (1973) Role of cyclic AMP and CA++, mechanical and metabolic events in isometrically contracting vascular smooth muscle. Acta Physiol Scand 87: 84–95PubMedCrossRefGoogle Scholar
  119. 119.
    Numano F, Watanabe Y, Takano K, Takano T, Arita M, Numano F, Maezawa H, Shimamoto T, Adachi K (1976) Microassay of cyclic nucleotides in vessel wall. I cyclic AMP. Exp Mol Pathol 25: 172–181Google Scholar
  120. 120.
    Burleigh MC, Barrett AJ, Lazarus GS (1974) Cathepsin Bl. A lysosomal enzyme that degrades native collagen. Biochem J 137: 387–398Google Scholar
  121. 121.
    Butler LG (1971) Yeast and other inorganic pyrophosphatases. In: Boyer PD (ed) The enzymes, vol IV, 3rd edn. Academic Press, New York, pp 529–541Google Scholar
  122. 122.
    Graves DJ, Wang JH (1972) a-Glucan phosphorylases. In: Boyer PD (ed) The enzymes, vol VII, 3rd edn. Academic Press, New York, pp 435–482Google Scholar
  123. 123.
    Kayne FJ (1973) Pyruvate kinase. In: Boyer PD (ed) The enzymes, vol VIII, 3rd edn. Academic Press, New York, pp 353–382Google Scholar
  124. 124.
    Winterbourne CC, Hawkins RE, Brian M, Carrell RW (1975) The estimation of red cell superoxide dismutase activity. J Lab Clin Med 85: 337–341Google Scholar
  125. 125.
    Packham MA, Cazenave JP, Kinlough-Rathbone RL, Mustard JF (1978) Drug effects on platelet adherence to collagen and damaged vessel walls. Adv Exp Med Biol 109: 253–276PubMedGoogle Scholar
  126. 126.
    Hellman B, Sehlin J, Taljedal IB (1976) Calcium and secretion: distinction between 2 pools of glucose-sensitive calcium in pancreatic islets. Science 194: 1421–1423PubMedCrossRefGoogle Scholar
  127. 127.
    Boucek MM, Snyderman R (1976) Calcium influx requirement for human neutrophil chemotoxis inhibition by lanthanum chloride. Science 193: 905–907PubMedCrossRefGoogle Scholar
  128. 128.
    Fassina G (1978) Mechanisms of lipomobilization. Adv Exp Med Biol 109: 209–223PubMedGoogle Scholar
  129. 129.
    Levy RJ, Lian JB, Gallop P (1979) Atherocalcin, a y-carboxyglutamic acid containing protein from atherosclerotic plaque. Biochem Biophys Res Commun 91: 41–49PubMedCrossRefGoogle Scholar
  130. 130.
    Levy RJ, Gundberg CM (1981) The presence of the bone specific protein, osteocalcin, in calcified atherosclerotic plaque and mineralized heart valves. Circulation 64, Suppl IV: 44Google Scholar
  131. 131.
    Deyl Z, Macek K, Vancikova O, Adam M (1979) The presence of y-carboxyglutamic acid-containing protein in atheromatous aortae. Biochim Biophys Acta 581: 307–315PubMedGoogle Scholar
  132. 132.
    Lian JB, Prien EL Jr, Glimcher MJ, Gallop PM (1977) The presence of protein-bound y-carboxyglutamic acid in calcium-containing renal calculi. J Clin Invest 59: 1151–1157PubMedCrossRefGoogle Scholar
  133. 133.
    Gerrity RG (1981) Migration of foam cells from atherosclerotic lesions. Am J Pathol 103: 191–200PubMedGoogle Scholar
  134. 134.
    Morland B, Morland J (1978) Selective induction of lysosomal enzyme activities in mouse peritoneal macrophages. J Reticuloendothel Soc 23: 469–477PubMedGoogle Scholar
  135. 135.
    Hibbs JR Jr (1976) The macrophage as a tumoricidal effector cell; a review of in vivo and in vitro studies on the mechanism of the activitated macrophage nonspecific cytotoxic reaction. In: Fink MA (ed) The macrophage in neoplasia. Academic Press, New York, pp 83–111Google Scholar
  136. 136.
    MacKaness GB (1967) The relationship of delayed hypersensitivity to acquired cellular resistance. Br Med Bull 23: 52–54PubMedGoogle Scholar
  137. 137.
    Murray M, Morrison WI (1979) Nonspecific induction of increased resistance in mice to Trypanosoma congolense and Trypanosoma brucei by immuno stimulants. Parasitology 79: 349–366PubMedCrossRefGoogle Scholar
  138. 138.
    Whittaker JA, Slater AJ (1977) The immunotherapy of acute myelogenous leukaemia using intravenous BCG. Br J Haematol 35: 263–273PubMedCrossRefGoogle Scholar
  139. 139.
    McKneally MF, Mayer C, Kausel HW, Alley RD (1976) Regional immunotherapy with intrapleural BCG for lung cancer. Surgical considerations. J Thorac Cardiovasc Surg 72: 333–338Google Scholar
  140. 140.
    Ross R, Glomset J (1973) Atherosclerosis and the arterial smooth muscle cell. Science 180: 1332–1339PubMedCrossRefGoogle Scholar
  141. 141.
    Ross R, Glomset J (1976) The pathogenesis of atherosclerosis. N Engl J Med 295: 369–377PubMedCrossRefGoogle Scholar
  142. 142.
    Ross R, Harker L (1976) Hyperlipidemia and atherosclerosis. Science 193: 1094–1100PubMedCrossRefGoogle Scholar
  143. 143.
    Fischer-Dzoga K, Fraser R, Wissler RW (1976) Stimulation of proliferation in stationary primary cultures of monkey and rabbit aortic smooth muscle cells: 1. Effects of lipoprotein fractions of hyperlipemic serum and lymph. Exp Mol Pathol 24: 346–359Google Scholar
  144. 144.
    Mustard JF, Glynn MF, Jorgensen L, Nishizawa BE, Packham MA, Rowsell HC (1968) Recent advances in platelets, blood coagulation factors and thrombosis. In: Miras LJ, Howard AN, Paoletti R (eds) Progress in biochemical pharmacology, vol 4. Plenum, New York, pp 508–532Google Scholar
  145. 145.
    Mustard JF, Packham MA, Rowsell HC, Jorgensen L (1968) The role of thrombogenic factors in atherosclerosis. Ann NY Acad Sci 149: 848–859PubMedCrossRefGoogle Scholar
  146. 146.
    Ross R, Vogel A (1978) The platelet-derived growth factor. Cell 14: 203–210PubMedCrossRefGoogle Scholar
  147. 147.
    Benditt EP, Benditt JM (1973) Evidence for a monoclonal origin of human atherosclerotic plaques. Proc Natl Acad Sci 70: 1753–1756PubMedCrossRefGoogle Scholar
  148. 148.
    Thomas WA, Reiner JM, Florentin RA, Janakidevi K, Lee KT (1977) Arterial smooth muscle cells in atherogenesis: births, deaths and clonal phenomena. In: Schlettler G, Goto G, Hata Y, Klose G (eds) Atherosclerosis IV. Springer-Verlag, New York, pp 16–23Google Scholar
  149. 149.
    Thomas WA, Janakidevi K, Florentin RA, Reiner JM (1978) The reversibility of the human atherosclerotic plaque. In: Hauss WH, Wissler RW, Lehman R (eds) International symposium: state of prevention and therapy in human arteriosclerosis and in animal models. Westdeutscher Verlag, Opladen, pp 73–80Google Scholar

Copyright information

© Springer-Verlag New York Inc. 1983

Authors and Affiliations

  • Assaad S. Daoud
  • Katherine E. Fritz
  • John Jarmolych
  • Mark L. Armstrong

There are no affiliations available

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