Metabolism of Fibromuscular and Atheromatous Plaques in an Experimental Model: Causal Mechanisms for the Development of Intimal Necrosis

Part of the Current Topics in Pathology book series (CT PATHOLOGY, volume 87)


Hallmarks in the development of atherosclerosis are intimal accumulation of leukocytes, especially monocytes/macrophages, proliferation of cells characterized as modified smooth muscle cells, formation of extracellular matrix, and incorporation of lipids either within intimal cells or associated with extracellular material (for reviews see: Hauss 1973; Geer and Webster 1974; Ross and Glomset 1976; Camejo 1982; Gotlieb 1982; Klurfeld 1983; Thomas and Kim 1983; Ross 1986; Munro and Cotran 1988; Stary 1990).


Arterial Wall Atheromatous Plaque Rabbit Aorta Human Atherosclerotic Plaque Intimal 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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adams CWM (1967) Vascular histochemistry in relation to the chemical and structural pathology of cardiovascular disease. Lloyd-Luke, LondonGoogle Scholar
  2. Apfel H, Betz E (1985) Der elektrische Widerstand von Arterienwänden bei Atheromentwicklung. Angio Arch 7:91–93Google Scholar
  3. Arnqvist HJ, Lundholm L (1976) Influence of oxygen tension on the metabolism of vascular smooth muscle:demonstration of a Pasteur effect. Atherosclerosis 25:245–252PubMedGoogle Scholar
  4. Avogaro P, Bittolo Bon G, Cazzolato G (1988) Presence of a modified low density lipoprotein in humans. Arteriosclerosis 8:79–87PubMedGoogle Scholar
  5. Badwey JA, Karnowsky M (1980) Active oxygen species and the function of phagocytotic leukocytes. Annu Rev Biochem 49:695–726PubMedGoogle Scholar
  6. Bayliss High OB, Adams CWM (1980) The role of macrophages and giant cells in advanced human atherosclerosis. Atherosclerosis 36:441–447Google Scholar
  7. Bergmeyer HU (ed) (1974) Methoden der enzymatischen Analyse. Verlag Chemie, Weinheim, pp 2178–2182Google Scholar
  8. Betz E (1991) Animal models and cultures of vessel wall cells in atherosclerosis research. Z Kardiol 80 [Suppl] 917–13Google Scholar
  9. Betz E Hämmerle H (1984) The action of antiatherogenic drugs on the development of atheroma and on cultures of smooth muscle cells and fibroblasts. Funkt Biol Med 3:46–55Google Scholar
  10. Betz E, Schlote W (1979) Responses of vessel walls to chronically applied electrical stimuli. Basic Res Cardiol 74:10–20PubMedGoogle Scholar
  11. Betz E, Wiegel W (1982) Smooth muscle hypersensitivity to norepinephrine of atheromatous proliferates in carotid arteries. In: Heisted DD, Marcus MC (eds) Cerebral blood flow. Effects of nerves and neurotransmitters. Elsevier/North-Holland, Amsterdam, pp 177–182Google Scholar
  12. Betz E, Roth J, Schlote W (1980) Proliferation of smooth muscle cells in long-term local stimulation of carotid arteries. Folia Angiol 28:28–31Google Scholar
  13. Björnheden T, Bondjers G (1987) Oxygen consumption in aortic tissue from rabbits with diet induced atherosclerosis. Arteriosclerosis 7:238–247PubMedGoogle Scholar
  14. Bowen-Pope DF, Ross R, Seifert RA (1985) Locally acting growth factors for vascular smooth muscle cells:endogenous synthesis and release from platelets. Circulation 72:735–740PubMedGoogle Scholar
  15. Camejo G (1982) The interactions of lipids and lipoproteins with the extracellular matrix of arterial tissue:its possible role in atherogenesis. Adv Lipid Res 19:1–53PubMedGoogle Scholar
  16. Cliff WJ, Heathcote CR, Moss NS, Reichenbach DD (1988) The coronary arteries in cases of cardiac and noncardiac sudden death. Am J Pathol 132:319–329PubMedGoogle Scholar
  17. Crawford DW, Blankenhorn DH (1991) Arterial wall oxygenation, oxyradicals, and atherosclerosis. Atherosclerosis 89:97–108PubMedGoogle Scholar
  18. Davies MJ, Woolf N, Rowlews PM, Pepper J (1988) Morphology of the endothelium over atherosclerotic plaques in human coronary arteries. Br Heart J 60:459–464PubMedGoogle Scholar
  19. Davies PF (1986) Vascular cell interactions with special reference to the pathogenesis of atherosclerosis. Lab Invest 55:5–21PubMedGoogle Scholar
  20. Doerr W (1978) Arteriosclerosis without end. Principles of pathogenesis and an attempt at a nosologic classification. Virchows Arch [A] 380:91–106Google Scholar
  21. Drake TA, Hannani K, Fei HH, Lavi S, Berliner JA (1991) Minimally oxidized low density lipoprotein induces tissue factor expression in cultured human endothelial cells. Am J Pathol 138:601–607PubMedGoogle Scholar
  22. Eitel W, Schmid G, Schlote W, Betz E (1980) Early arteriosclerotic changes of the carotid artery wall induced by electrostimulation. A study by scanning and transmission electron microscopy. Pathol Res Pract 170:211–229PubMedGoogle Scholar
  23. Engel E, Knehr HE, Betz E (1984) Messungen des Sauerstoffverbrauchs von Arterienwandelementen. Funktionsanalyse biologischer Systeme 12:83–89Google Scholar
  24. Esterbauer H, Jürgens G, Quehenberger O, Koller E (1987) Autoxidation of human low density lipoprotein:loss of polyunsaturated fatty acids and vitamin E on generation of aldehydes. J Lipid Res 28:495–509PubMedGoogle Scholar
  25. Faupel RP, Seitz HJ, Tarnowsky W, Thiemann V, Weiß CH (1972) The problem of tissue sampling from experimental animals with respect to freezing technique, anoxia, stress, and narcosis. Arch Biochem Biophys 148:509–522PubMedGoogle Scholar
  26. Ferns GAA, Raines EW, Sprugel KH, Motani AS, Reidy MA, Ross R (1991) Inhibition of smooth muscle accumulation after angioplasty by an antibody to PDGF. Science 253:1129–1132PubMedGoogle Scholar
  27. Geer JC, Webster WS (1974) Morphology of mesenchymal elements of normal artery, fatty streaks and plaques. Adv Exp Med Biol 43:9–33PubMedGoogle Scholar
  28. Glavind J, Hartmann S, Clemmesen J, Jessen KE, Dam H (1952) Studies of the role of lipoperoxides in human pathology. Acta Pathol Microbiol Scand 30:1–6PubMedGoogle Scholar
  29. Gotlieb AJ (1982) Smooth muscle and endothelial cell function in the pathogensis of atherosclerosis. Can Med Assoc J 126:903–908PubMedGoogle Scholar
  30. Gutstein WH, Harrison J, Parl F, Kin G, Avitable M (1978) Neuronal factors contribute to atherogenesis. Science 199:449–451PubMedGoogle Scholar
  31. Hajjar DP, Farber IC, Smith SC (1988) Oxygen tension within the arterial wall:relationship to altered bioenergetic metabolism and lipid accumulation. Arch Biochem Biophys 262:375–380PubMedGoogle Scholar
  32. Hansson GK, Jonasson L, Holm J, Clowes MM, Clowes AW (1988) Gamma-interferon regulates vascular smooth muscle proliferation and Ia antigen expression in vivo and in vitro. Circ Res 63:712–719PubMedGoogle Scholar
  33. Hansson GK, Holm J, Jonasson L (1989) Detection of activated T-lymphocytes in the human atherosclerotic plaque. Am J Pathol 135:169–175PubMedGoogle Scholar
  34. Harats D, Bennaim M, Dabach Y, Hollander G, Havivi E, Stein O, Stein Y (1990) Effects of vitamin C and vitamin E supplementation on susceptibility of plasma lipoproteins to peroxidation induced by acute smoking. Atherosclerosis 85:47–54Google Scholar
  35. Hauss WH (1973) Über die Rolle des Mesenchyms in der Genese der Arteriosklerose. Virchows Arch [A] 359:135–156Google Scholar
  36. Haust MD (1974) Light and electron microscopy of human atherosclerotic lesions. Adv Exp Med Biol 104:33–59Google Scholar
  37. Heinle H (1982) Peroxide induced activation of glycogen phosphorylase a activity in vascular smooth muscle. Biochem Biophys Res Commun 107:597–601PubMedGoogle Scholar
  38. Heinle H (1984) Vasoconstriction of carotid artery induced by hydroperoxides. Arch Int Physiol Biochem 92:267–271Google Scholar
  39. Heinle H (1985) Stoffwechseländerungen der Gefäßwand bei experimenteller Arteriosklerose. Habilitations schrift, University of TübingenGoogle Scholar
  40. Heinle H (1987) Metabolite concentration gradients in the arterial wall of experimental atherosclerosis. Exp Mol Pathol 46:312–320PubMedGoogle Scholar
  41. Heinle H (1989) Influence of oxidative stress on metabolic and contractile functions of arterial smooth muscle. In: Acker H (ed) Oxygen sensing in tissues. Springer, Berlin Heidelberg New York, pp 151–164Google Scholar
  42. Heinle H, Liebich H (1980) The influence of diet-induced hypercholesterolemia on the degree of oxidation of glutathione in rabbit aorta Atherosclerosis 37:637–640PubMedGoogle Scholar
  43. Heinle H, Knehr H, Schmid G, Eitel W Betz E (1980a) Biochemical variations in electrically induced intimai smooth muscle cell proliferates of the rabbit carotid artery. Artery 8:393–397PubMedGoogle Scholar
  44. Heinle H, Tarozy M, Schmid G, Betz E (1980b) Morphological and functional alterations in the arterial wall after local electrical stimulation. Bibl Anat 20:79–82Google Scholar
  45. Heinle H, Stowasser F, Betz. E (1982) Metabolic changes in modified smooth muscle cells of rabbit carotid arteries. Basic Res Cardiol 77:82–92PubMedGoogle Scholar
  46. Heinle H, Kling D, Lindner V (1987) Increased contractile responses of isolated arteriosclerotic rabbit carotid arteries to various vasoactive stimuli. Int Angiol 6:53–58PubMedGoogle Scholar
  47. Heinle H, Tries S, Esterbauer H (1988) Effects of H2O2, arachidonic acid hydroperoxide and 4-hydroxynonenal on arterial smooth muscle contraction. Pflügers Arch 412 [Suppl]:R85Google Scholar
  48. Heinle H, Ableiter H, Betz E (1991a) Diet-induced hypercholesterolemia decreases osmotic resistance of rabbit erythrocytes:possible involvement of the thiol-protecting system. Nutr Metab Cardiovasc Dis 1:125–129Google Scholar
  49. Heinle H, Veigel C, Tries S (1991b) The influence of oxidatively modified low density lipoprotein on parameters of energy metabolism and contractile function of arterial smooth muscle. Free Radic Res Commun 11:281–286PubMedGoogle Scholar
  50. Heughan C, Niinikoshi J, Hunt TK (1973) Oxygen tension in lesions of experimental atherosclerosis of rabbits. Atherosclerosis 17:361–367PubMedGoogle Scholar
  51. Hort W (1985) Morphologie der koronaren Herzerkrankung. In: Schettler G, Gross R (eds) Arteriosklerose:Grundlagen, Diagnostik, Therapie. Deutscher Ärzte Verlag, Cologne, pp 35–44Google Scholar
  52. Hort W, Kalbfleisch H, Frenzel H (1982) Coronary atherosclerosis and its relation to myocardial infarction. Verh Dtsch Ges Inn Med 88:1298–1301Google Scholar
  53. Hunt JV, Wolff SP (1991) Oxidative glycation and free radical production—a causal mechanism of diabetic complication. Free Radic Res Commun 12:115–123PubMedGoogle Scholar
  54. Jonasson L, Holm J, Skalli O, Bondjers G, Hansson GK (1986) Regional accumulations of T cells, macrophages, and smooth muscle cells in human atherosclerotic plaque. Arteriosclerosis 6:131–138PubMedGoogle Scholar
  55. Jurrus ER, Weiss HS (1977) In vitro oxygen tensions in the rabbit aortic arch. Atherosclerosis 28:223–232PubMedGoogle Scholar
  56. Kirk JE (1963) Intermediary metabolism of human arterial tissue and its change with age and atherosclerosis. In: Sandler M, Bourne GH (eds) Atherosclerosis and its origin. Academic Press, New York, pp 67–117Google Scholar
  57. Kirsch WM, Ferguson JF, Ignelzi R (1978) Regional differences in arterial metabolic rates:its significance in relation to cerebral vasospasm. Adv Neurol 20:47–57PubMedGoogle Scholar
  58. Kling D, Holzschuh T, Betz E (1987a) Temporal sequence of morphological alterations in artery walls during experimental atherogenesis. Occurrence of leukocytes. Res Exp Med 187:237–250Google Scholar
  59. Kling D, Holzschuh T, Strohschneider T, Betz E (1987b) Enhanced endothelial permeability and invasion of leukocytes into the artery wall as inital events in experimental atherosclerosis. Int Angiol 6:21–28PubMedGoogle Scholar
  60. Kling D, Heinle H, Harlan JM (1991) Participation of leukocytes in the development of experimentally induced arteriosclerosis. Morphological and functional aspects. In: Hauss WH, Wissler RW, Bauch HJ (eds) Abhandlungen der Rhein. Westf. Akademie der Wissenschaften, Westdeutscher Verlag, pp 105–115Google Scholar
  61. Klurfeld DM (1983) Interactions of immune function with lipids and atherosclerosis. CRC Crit Rev Toxicol 11:333–365Google Scholar
  62. Knehr HE, Heinle H, Betz E (1980) Enhanced oxygen uptake and lactate production of smooth mucsle cell proliferates of rabbit carotid arteries. Pflügers Arch 387:73–77PubMedGoogle Scholar
  63. Loeper J, Emerit J, Goy J, Bedu O, Loeper J (1983) Lipid peroxidation during human atherosclerosis. IRCS Med Sci 11:1034–1035Google Scholar
  64. Lowry DH, Passonneau JV (1972) A flexible system of enzymatic analysis. Academic, New YorkGoogle Scholar
  65. Lynch RM, Paul RJ (1983) Compartmentation of glycolytic and glycogenolytic metabolism in vascular smooth muscle. Science 222:1344–1346PubMedGoogle Scholar
  66. Morrison AD, Berwick L, Orci L, Winegrad AI (1976) Morphology and metabolism of an aortic intima-media preparation in which an intact endothelium is preserved. J Clin Invest 57:650–660PubMedGoogle Scholar
  67. Morrison ES, Scott RF, Kroms M, Frick J (1972) Glucose degradation in normal and atherosclerotic aortic intima-media. Atherosclerosis 16:175–184PubMedGoogle Scholar
  68. Moss AJ, Samuelson P, Angell C, Minken SL (1968) Polarographic evaluation of transmural oxygen availability in intact muscular arteries. J Atheroscler Res 8:803–810PubMedGoogle Scholar
  69. Mowri H, Chinen K, Ohkuma S, Takano T (1986) Peroxidized lipids isolated by HPLC from atherosclerotic aorta. Biochem Int 12:347–352PubMedGoogle Scholar
  70. Munro MJ, Cotran RS (1988) The pathogenesis of atherogenesis:atherogenesis and inflammation. Lab Invest 58:249–261PubMedGoogle Scholar
  71. Munro AF, Rifkind BM, Leibescheutz HJ, Campbell RSF, Howard BR (1961) Effect of cholesterol feeding on the oxygen consumption of aortic tissue from the cockerel and the rat. J Atheroscler Res 1:296–304PubMedGoogle Scholar
  72. Nathan CF (1987) Secretory products of macrophages. J Clin Invest 79:319–326PubMedGoogle Scholar
  73. Niendorf A, Beisiegel U (1991) Low-density lipoprotein receptors. Curr Top Pathol 83:187–218PubMedGoogle Scholar
  74. Niinikoshi J, Heughan C, Hunt TK (1973) Oxygen tension in the aortic wall of normal rabbits. Atherosclerosis 17:353–359Google Scholar
  75. Nilsson J (1986) Growth factors and the pathogenesis of atherosclerosis. Atherosclerosis 62:185–199PubMedGoogle Scholar
  76. Nishigaki I, Hagihara M, Tsunekawa H, Maseki M, Yagi K (1981) Lipid peroxides levels of serum lipoprotein fractions of diabetic patients. Biochem Med 25:373–378PubMedGoogle Scholar
  77. Numano F, Yamaguchi S, Jaima M, Watabiki S, Sakurada S, Mashimo N, Maezawa H (1979) Microassay of adenine nucleotides in intima and media of the aortic wall. Exp Mol Pathol 31:468–478PubMedGoogle Scholar
  78. Odessy R, Chace KV (1982) Utilization of endogenous lipid, glycogen, and protein by rabbit aorta. Am J Physiol 243:H128–H132Google Scholar
  79. Paul RJ (1981) Chemical energetics of vascular smooth muscle. In: Bohr DF, Somlyo AP, Sparks H (eds) Handbook of physiology, Sect 2. The cardiovascular system, vol 2. Vascular smooth muscle. Williams & Wilkins, Baltimore, pp 201–235Google Scholar
  80. Paul RJ (1983) Functional compartmentalization of oxidative and glycolytic metabolism in vascular smooth muscle. Am J Physiol 244:C399–C409PubMedGoogle Scholar
  81. Peterson JW, Paul RJ (1974) Aerobic glycolysis in vascular smooth muscle:relation to isometric tension. Biochem Biophys Acta 357:167–176PubMedGoogle Scholar
  82. Quinn MT, Parthasarathy S, Fong LG, Steinberg D (1987) Oxidatively modified low density lipoproteins:a potential role in recruitment and retention of monocytes/macrophages during atherogenesis. Proc Natl Acad Sci USA 84:2995–2998PubMedGoogle Scholar
  83. Radi R, Beckmann JS, Bush KM, Freeman BA (1991) Peroxynitrite oxidation of sulfhydryls. The cytotoxic potential of superoxide and nitric oxide. J biol Chem 266:4244–4250PubMedGoogle Scholar
  84. Ridray S, Capron L, Hendes D, Picon L, Ktorza A (1991) Effects of fasting and refeeding on the proliferative response of rat aorta to injury. Am J Physiol 261:H190–H195PubMedGoogle Scholar
  85. Rosenfeld ME (1991) Oxidized LDL affects multiple atherogenic cellular responses. Circulation 83:2137–2140PubMedGoogle Scholar
  86. Ross R (1986) The pathogenesis of atherosclerosis—an update. N Engl J Med 314:488–500PubMedGoogle Scholar
  87. Ross R, Glomset JA (1976) The pathogenesis of atherosclerosis. N Engl J Med 295:369–377, 420–425Google Scholar
  88. Ross R, Raines E, Bowen Pope DF (1982) Growth factors from platelets, monocytes, and endothelium:their role in the cell proliferation. Ann NY Acad Sci 397:18–24PubMedGoogle Scholar
  89. Ross R, Raines EW, Bowen Pope DF (1986) The biology of platelet derived growth factor. Cell 46:155–158PubMedGoogle Scholar
  90. Schlote W, Boellard JW, Betz E (1980) Experimental atherosclerosis—the animal model and its relation to the human disease. Folia Angiol 28:76–79Google Scholar
  91. Schneiderman G, Goldstick TK (1978) Carbon monoxide-induced arterial wall hypoxia and arteriosclerosis. Atherosclerosis 30:1–15PubMedGoogle Scholar
  92. Schwartz SM, Campbell GR, Campbell JH (1986) Replication of smooth muscle cells in vascular disease. Circ Res 58:427–444PubMedGoogle Scholar
  93. Scott RF, Daoud AS, Wortmen B, Morrison ES, Jarmolych J (1966) Proliferation and necrosis in coronary and cerebral arteries. J Atheroscler Res 6:499–505Google Scholar
  94. Scott RF, Morrison ES, Kroms M (1970) Effect of cold shock on respiration and glycolysis in swine arterial tissue. Am J Physiol 219:1363–1365PubMedGoogle Scholar
  95. Smith EB (1982) Metabolism of the arterial wall. In: Born GRV, Catapano AL, Paoletti R (eds) Factors in formation and regression of the atherosclerotic plaque. Plenum, New York, pp 21–33Google Scholar
  96. Solberg LA, Strong JP (1983) Risk factors and atherosclerotic lesions. A review of autopsy studies. Arteriosclerosis 3:187–198PubMedGoogle Scholar
  97. Stange E, Papenberg J (1978) Changes in chemical and metabolic properties of rabbit aorta by dietary cholesterol, and saturated and polyunsaturated fats. Atherosclerosis 29:467–476PubMedGoogle Scholar
  98. Stary HC (1990) The sequence of cells and matrix changes in atherosclerotic lesions of coronary arteries in the first years of life. Eur Heart J 11 [Suppl E]:3–19PubMedGoogle Scholar
  99. St. Clair RW (1976) Metabolism of the arterial wall and atherosclerosis. Atherosclerosis Rev 1:61–118Google Scholar
  100. Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL (1989) Beyond cholesterol:modifications of low density lipoprotein that increase its atherogenicity. N Engl J Med 320:915–924PubMedGoogle Scholar
  101. Steinbrecher UP, Zhang H, Lougheed M (1990) Role of modified LDL in atherosclerosis. Free Radic Biol Med 9:155–168PubMedGoogle Scholar
  102. Tanner FC, Noll G, Boulanger CM, Löscher TA (1991) Oxidized low density lipoproteins inhibit relaxations of porcine coronary arteries—role of scavenger receptor and endothelium-derived nitric oxide. Circulation 83:2012–2020PubMedGoogle Scholar
  103. Tarczy M, Heinle H, Lindner V (1981) Early changes of vascular permeability after electrical stimulation of the common carotid artery. Pflügers Arch 389 [Suppl]:R17Google Scholar
  104. Thomas WA, Kim DN (1983) Atherosclerosis as a hyperplastic and/or neoplastic process. Lab Invest 48:245–255PubMedGoogle Scholar
  105. Tries S (1990) Reaktionen der Gefäßwand unter atherogenen Reizen and therapeutischen Eingriffen:Untersuchungen zum Einfluß von Peroxidationsprodukten des LDL bzw. von Ballon-Angioplastie auf die Arteria carotis des Kaninchens. Thesis, University of TübingenGoogle Scholar
  106. Trimm JL, Salama G, Abramson JJ (1986) Sulfhydryl oxidation induces rapid calcium release from sarcoplasmic reticulum vesicles. J Biol Chem 261:16092–16099PubMedGoogle Scholar
  107. Tsai AC, Chen NSC (1979) Effect of cholesterol-feeding on tissue glucose uptake, insulin-degradation, serum lipids and serum lipoperoxide levels in rabbits. J Nutr 109:606–612PubMedGoogle Scholar
  108. Velican C, Velican D (1982) Atherosclerotic involvement of human intracranial arteries with special references to intimai necrosis. Atherosclerosis 43:59–69PubMedGoogle Scholar
  109. Wiegel WB (1985) Aktive und passive mechanische Eigenschaften atheromatöser Proliferate der Arteria carotis bei Kaninchen. Thesis, University of TübingenGoogle Scholar
  110. Wissler RW, Vesselinovitsch D, Getz GS (1976) Abnormalities of the arterial wall and its metabolism in atherogenesis. Prog Cardiovasc Dis 18:341–369PubMedGoogle Scholar
  111. Wolff SP, Jiang ZY, Hunt JV (1991) Protein glycation and oxidative stress in diabetes mellitus and ageing. Free Radic Biol Med 10:339–352PubMedGoogle Scholar
  112. Zemplenyi T (1974) Vascular enzymes and the relevance of their study to problems of atherogenesis. Med Clin North Am 58:293–321PubMedGoogle Scholar
  113. Zemplenyi T (1977) Metabolic intermediates, enzymes and lysosomal activity in aortas of spontaneously hypertensive rats. Atherosclerosis 28:233–246PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

There are no affiliations available

Personalised recommendations