Skip to main content

Pathobiology of Atherosclerosis

  • Chapter
  • 127 Accesses

Part of the book series: Basic Science for the Cardiologist ((BASC,volume 1))

Abstract

Developments in characterizing the cellular components of the atherosclerotic plaque [1] and in the description of its natural history [2, 3] give a better knowledge of the agents of atherogenesis. Histologically, the foam cells of the fatty streak which characterizes the plaque at an early stage are derived from macrophages (see Stary’s classification below). At a later stage the lipidic mass is covered with a fibrous tissue which is mainly made of smooth muscle cells, and thus forms the fibrolipidic plaque. Rather large amounts of T-lymphocytes - about 20% - are found as well, surrounding the plaque and in the fibrous cap [4]. The hypothesis of a primary endothelial lesion appearing before the inflammatory recruitment does not seem to be correct. The endothelium actually remains morphologically intact during the development of atherosclerosis, although it is activated and directly involved in the immuno-inflammatory response. The response develops once plasma LDL have first accumulated in the intima and have been oxidized (by free radicals, endothelial cells, smooth muscle cells or macrophages). Modified LDL are then recognized by the scavenger receptors (SR) expressed on the macrophage surface. These receptors, including type I and II class A SR [5], CD36 [6], the Fc receptor γ RII-B2 for IgG [7], SR-BI [8] and CD68 [9, 10], can internalize high levels of modified LDL because they are not negatively controlled when the intracellular concentration of cholesterol increases [11].

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Jonasson L, Holin J, Skalli O, Bondjers G, Hansson GK.. Regional accumulations of T cells, macrophages and smooth muscle cells in the human atherosclerotic plaque. Arteriosclerosis. 1986;6:131–138.

    PubMed  CAS  Google Scholar 

  2. Stary HC, Chandler AB, Glagov S, Guyton JR, Insull W Jr, Rosenfeld ME, Schaffer SA, Schwartz CJ, Wagner WD, Wissler RW. A definition of initial, fatty streak, and intermediate lesions of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation. 1994;89:2462–2478.

    PubMed  CAS  Google Scholar 

  3. Stary HC, Chandler AB, Dinsmore RE, Fuster V, Glagov S, Insull W Jr, Rosenfeld ME, Schwartz CJ, Wagner WD, Wissler RW. A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation. 1995; 92:1355–1374.

    PubMed  CAS  Google Scholar 

  4. Hansson GK, Holin J, Jonasson L. Detection of activated T lymphocytes in the human atherosclerotic plaque. Am J Pathol. 1989;135:169–175.

    PubMed  CAS  Google Scholar 

  5. Resnick D, Chatterton JE, Schwartz K, Slayter H, Krieger M J. Structures of class A macrophage scavenger receptors. Electron microscopic study of flexible, multidomain, fibrous proteins and determination of the disulfide bond pattern of the scavenger receptor cysteine-rich domain. J Biol Chem. 1996;271:26924–26930.

    PubMed  CAS  Google Scholar 

  6. Endemann G, Stanton LW, Madden KS, Bryant CM, White RT, Protter AA. CD36 is a receptor for oxidized low density lipoprotein. J Biol Chem. 1993;268:11811–11816.

    PubMed  CAS  Google Scholar 

  7. Stanton LW, White RT, Bryant CM, Protter AA, Endemann G. A macrophage Fc receptor for IgG is also a receptor for oxidized low density lipoprotein. J Biol Chem. 1992;267:22446–22451.

    PubMed  CAS  Google Scholar 

  8. Acton S, Rigotti A, Landschulz KT, Xu S, Hobbs HH, Krieger M. Identification of scavenger receptor SR-BI as a high density lipoprotein receptor. Science. 1996;271:518–520.

    PubMed  CAS  Google Scholar 

  9. Ramprasad MP, Fischer W, Witztum JL, Sambrano GR, Quehenberger O, Steinberg D. The 94-to 97-kDa mouse macrophage membrane protein that recognizes oxidized low density lipoprotein and phosphatidylserine-rich liposomes is identical to macrosialin, the mouse homologue of human CD68. Proc Natl Acad Sci U S A. 1995;92:9580–9584.

    PubMed  CAS  Google Scholar 

  10. Ramprasad MP, Terpstra V, Kondratenko N, Quehenberger O, Steinberg D. Cell surface expression of mouse macrosialin and human CD68 and their role as macrophage receptors for oxidized low density lipoprotein. Proc Natl Acad Sci USA. 1996;93:14833 14838.

    PubMed  Google Scholar 

  11. Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztuin JL. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med. 1989;320:915–924.

    PubMed  CAS  Google Scholar 

  12. Anitschkow N, Chalatow S. Über experimentelle cholesterin-steatose und ihre bedeutung für die entstechung einiger pathologishen prozesses. Zentrablatt für Allgemeine Pathologie und Pathologishe Anatomie, vol 24(1), 1913, p 1–9. Translated in Arteriosclerosis. 1983;3:178–182, entitled: On experimental cholesterin steatosis and its significance in the origin of some pathological processes.

    Google Scholar 

  13. Page IH. Atherosclerosis. An introduction. Circulation. 1954;10:1–27.

    PubMed  CAS  Google Scholar 

  14. Smith EB, Slater R. The chemical and immunological assay of low density lipoproteins extracted from human thoracic aortic intima. Atherosclerosis. 1970;11:417–438.

    PubMed  CAS  Google Scholar 

  15. Hoff HF, Heideman CL, Gaubatz JW, Titus JL, Gotto AM. Quantification of apo-B in human aortic fatty streaks. Atherosclerosis. 1978;30:263–272.

    PubMed  CAS  Google Scholar 

  16. Schwenke DC, Carew TE. Initiation of atherosclerotic lesions in cholesterol-fed rabbits. I. Focal increases in arterial LDL concentrations precede development of fatty streaks lesions. Arteriosclerosis. 1989;9:895–907.

    PubMed  CAS  Google Scholar 

  17. Curmi PA, Juan L, Tedgui A. Effect of transmural pressure on LDL and albumin transport and distribution across the intact arterial wall. Circ Res. 1990;66:1692–1702.

    PubMed  CAS  Google Scholar 

  18. Meyer G, Merval R, Tedgui A. Effects of pressure-induced wall stretching and convection on low density lipoprotein and albumin uptake in the rabbit aorta. Circ Res. 1996;79: 532–540.

    PubMed  CAS  Google Scholar 

  19. Nordestgaard BG, Stender S, Kjeldsen K. Reduced atherogenesis in cholesterol-fed diabetic rabbits. Giant lipoproteins do not enter the arterial wall. Arteriosclerosis. 1988;8:421–428.

    PubMed  CAS  Google Scholar 

  20. Napoli C, D’Armiento FP, Mancini FP, Postiglione A, Witztum JL, Palumbo G, Palinski W. Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimai accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions. J Clin Invest. 1997;100:2680–2690.

    PubMed  CAS  Google Scholar 

  21. Ross R. 1993. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 362:801–809.

    PubMed  CAS  Google Scholar 

  22. Libby P, Hansson GK. Biology of disease. Involvement of the immune system in human atherogenesis; current knowledge and unanswered questions. Lab Invest. 1991;64:5–15.

    PubMed  CAS  Google Scholar 

  23. Smith JD, Trogan E, Ginsberg M, Grigaux C, Tian J, Miyata M. Decreased atherosclerosis in mice deficient in both macrophage colony-stimulating factor (op) and apolipoprotein E. Proc Natl Acad Sci USA. 1995;92:8264–8268.

    PubMed  CAS  Google Scholar 

  24. Qiao JH, Tripathi J, Mishra NK, Cai Y, Tripathi S, Wang XP, Imes S, Fishbein MC, Clinton SK, Libby P, Lusis AJ, Rajavashisth TB. Role of macrophage colony-stimulating factor in atherosclerosis: studies of osteopetrotic mice. Am J Pathol. 1997;150:1687–1699.

    PubMed  CAS  Google Scholar 

  25. Rajavashisth T, Qiao JH, Tripathi S, Tripathi J, Mishra N, Hua M, Wang XP, Loussararian A, Clinton S, Libby P, Lusis A. Heterozygous osteopetrotic (op) mutation reduces atherosclerosis in LDL receptor-deficient mice. J Clin Invest. 1998;101:2702–2710.

    PubMed  CAS  Google Scholar 

  26. Suzuki H, Kurihara Y, Takeya M, Kamada N, Kataoka M, Jishage K, Ueda O, Sakaguchi H, Higashi T, Suzuki T, Takashima Y, Kawabe Y, Cynshi O, Wada Y, Honda M, et al. A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection. Nature. 1997;386:292–296.

    PubMed  CAS  Google Scholar 

  27. Ross R, Masuda J, Paines EW, Gown AM, Katuda S, Sasahara M, Maiden LT, Masuko H, Sato H. Localization of PDGF-B protein in macrophages in all phases of atherogenesis. Science. 1990;248:1009–1012.

    PubMed  CAS  Google Scholar 

  28. Wilcox JN, Smith KM, Williams LT, Schwartz SM, Gordon D. Platelet derived growth factor mRNA detection in human atherosclerotic plaques by in situ hybridization. J Clin Invest. 1988; 82:1134–1143.

    PubMed  CAS  Google Scholar 

  29. Liptay MJ, Parks WC, Mecham RP, Roby J, Kaiser LR, Cooper JD, Botney MD. Neointimal macrophages colocalize with extracellular matrix gene expression in human atherosclerotic pulmonary arteries. J Clin Invest. 1993;91:588–594.

    PubMed  CAS  Google Scholar 

  30. Tipping PG, Hancock WW. Production of tumor necrosis factor and interleukin by macrophages from human atheromatous plaques. Am J Pathol. 1993;42:1121–1728.

    Google Scholar 

  31. Rosenfeld ME, Ross R. Macrophage and smooth muscle cell proliferation in atherosclerotic lesions of WHHL and comparably hypercholesterolemic fat-fed rabbits. Arteriosclerosis. 1990; 10:680–687.

    PubMed  CAS  Google Scholar 

  32. Clinton SK, Underwood R, Hayes L, Sherman ML, Kufe DW, Libby P. Macrophage colony-stimulating factor gene expression in vascular cells and in experimental and human atherosclerosis. Am J Pathol. 1992;140:301–316.

    PubMed  CAS  Google Scholar 

  33. Geng Y-J, Libby P. Evidence for apoptosis in advanced human atheroma. Colocalization with interleukin-1β-converting enzyme. Am J Pathol. 1995;147:251–266.

    PubMed  CAS  Google Scholar 

  34. Isner JM, Kearney M, Bortman S, Passen J. Apoptosis in human atherosclerosis and restenosis. Circulation. 1995;91:2703–2711.

    PubMed  CAS  Google Scholar 

  35. Han DKM, Haudenschild CC, Hong MK, Tinkle BT, Leon MB, Liau G. Evidence for apoptosis in human atherogenesis and in a rat vascular injury model. Am J Pathol. 1995;147:267–277.

    PubMed  CAS  Google Scholar 

  36. Björkerud S, Björkerud B. Apoptosis is abundant in human atherosclerotic lesions, especially in inflammatory cells (macrophages and T cells), and may contribute to the accumulation of gruel and plaque instability. Am J Pathol. 1996;149:367–380.

    PubMed  Google Scholar 

  37. Mallat Z, Ohan J, Lesèche G, Tedgui A. Colocalization of CPP-32 with apoptotic cells in human atherosclerotic plaques. Circulation. 1997;96:424–428.

    PubMed  CAS  Google Scholar 

  38. Kockx MM, De Meyer GR, Muhring J, Jacob W, Bult H, Herman AG. Apoptosis and related proteins indifferent stages of human atherosclerotic plaques. Circulation. 1998;97:2307–2315.

    PubMed  CAS  Google Scholar 

  39. Kleindiest, Xu Q, Willeit J, Waldenberger FR, Weimann, Wick G. Immunology of atherosclerosis. Demonstration of Heat Shock Protein 6 expression and T lymphocytes bearing α/β or γ/δ receptor in human atherosclerotic lesions. Am J Pathol. 1993;142:1927–1937.

    Google Scholar 

  40. Miller DD, Craig FE, Dressier FA, Aguirre FV, Farrar MA, Breland CM, Donohue TJ, Kern MJ, Bach RG. Immunohistochemical characterization of immune cell composition and cytokine receptor expression in human coronary atherectomy tissue. Coron Artery Dis. 1995;6:965–972.

    PubMed  CAS  Google Scholar 

  41. Stemme S, Holm J, Hansson GK. T lymphoctes in human atherosclerotic plaques are memory cells expressing CD45RO and the integrin VLA-1. Arterioscler Thromb. 1992;12:206–211.

    PubMed  CAS  Google Scholar 

  42. Stemme S, Faber B, Holm J, Wiklund O, Witzum JL, Hansson GK. T lymphocytes from human atherosclerotic plaques recognize oxidized low density lipoprotein. Proc Nat Acad Sci USA. 1995;92:3893–3897.

    PubMed  CAS  Google Scholar 

  43. Xu Q, Willeit J, Marosi M, Kleindienst R, Oberhollenzer F, Kiechl S, Stulnig T, Luef G, Wick G. Association of serum antibodies to heat-shock protein 65 with carotid atherosclerosis. Lancet. 1993;341:255–259.

    PubMed  CAS  Google Scholar 

  44. Berberian PA, Myers W, Tytell M, Challa V, Bond MG. lmmununohistochemical localisation of heat shiock protein-70 in normal-appearing and atherosclerotic specimens of human arteries. Am J Pathol. 1990; 36:71–80.

    Google Scholar 

  45. Hansson GK. Immunological markers of atherosclerosis. Lancet, 1993; 341:278.

    PubMed  CAS  Google Scholar 

  46. Kol A, Sukhova GK, Lichtman AH, Libby P. Chlamydial heat shock protein 60 localizes in human atheroma and regulates macrophage tumor necrosis factor-α and matrix metalloproteinase expression. Circulation. 1998;98:300–307.

    PubMed  CAS  Google Scholar 

  47. Emeson EE, Shen ML. Accelerated atherosclerosis in hyperlipidemic C57BL/6 mice treated with cyclosporin A. Am J Pathol. 1993;142:1906–1915.

    PubMed  CAS  Google Scholar 

  48. Roselaar SE, Schonfeld G, Daugherty A. Enhanced development of atherosclerosis in cholesterol-fed rabbits by suppression of cell-mediated immunity. J Clin Invest. 1995;96:1389–1394.

    PubMed  CAS  Google Scholar 

  49. Drew AF, Tipping PG. Cyclosporine treatment reduces early atherosclerosis in the cholesterol-fed rabbit. Atherosclerosis. 1995;116:181–189.

    PubMed  CAS  Google Scholar 

  50. Emeson EE, Shen ML, Bell CG, Qureshi A. Inhibition of atherosclerosis in CD4 T-cell-ablated and nude (nu/nu) C57BL/6 hyperlipidemic mice. Am J Pathol. 1996;149:675–685.

    PubMed  CAS  Google Scholar 

  51. Fyfe A, Qiao JH, Lusis AJ. Immune-deficient mice develop typical atherosclerosis fatty streaks when fed an atherogenic diet. J Clin Invest. 1994;94:2516–2520.

    PubMed  CAS  Google Scholar 

  52. Daugherty A, Pure E, Delfel-Butteiger D, Chen S, Leferovich J, Roselaar SE, Rader DJ. The effects of total lymphocyte deficiency on the extent of atherosclerosis in apolipoprotein E-/-mice. J Clin Invest. 1997;100:1575–1580.

    PubMed  CAS  Google Scholar 

  53. Dansky HM, Charlton SA, Harper MM, Smith JD. T and B lymphocytes play a minor role in atherosclerotic plaque formation in the apolipoprotein E-deficient mouse. Proc Natl Acad Sci U S A. 1997;94:4642–4646.

    PubMed  CAS  Google Scholar 

  54. Amento EP, Ehsani N, Palmer H, Libby P. Cytokines positively and negatively regulate interstitial collagen gene expression in human smooth-muscle cells. Arteriosclerosis. 1991;11: 1223–1230.

    CAS  Google Scholar 

  55. Clinton SK, Libby P. Cytokines and growth factors in atherogenesis. Arch Pathol Lab Med. 1992;116:1292–1300.

    PubMed  CAS  Google Scholar 

  56. Kishikawa H, Shimokama T, Watanabe T. Localization of T lymphocytes and macrophages expressing IL-1, IL-2 receptor, IL-6 and TNF in human aortic intima. Role of cell-mediated immunity in human atherogenesis. Virchows Arch A Pathol Anat Histopathol. 1993;423:433–442.

    PubMed  CAS  Google Scholar 

  57. Seino Y, Ikeda U, Ikeda M, Hasegawa T, Misawa Y, Yamamoto K, Kano S, Shimada K. Interleukin 6 gene transcripts are expressed in human atherosclerotic lesions. Cytokine. 1994;6:87–91.

    PubMed  CAS  Google Scholar 

  58. Barath P, Fishleni MC, Cao J, Berenson J, Helfant RH, Forrester JS. Detection and localisation of tumor necrosis factor in human atheroma. Am J Cardiol. 1990; 65:297–302.

    PubMed  CAS  Google Scholar 

  59. Clinton SK, Fleet JC, Loppnow H, Salomon RN, Clark BD, Cannon JG, Shaw AR, Dinarello CA, Libby P. Interleukin-1 gene expression in rabbit vascular tissue in vivo. Am J Pathol 1991;138:1005–1014.

    PubMed  CAS  Google Scholar 

  60. Nelken NA, Coughlin SR, Gordon D, Wilcox JN. Monocyte chemoattractant protein-1 in human £theromatous plaques. J Clin Invest. 1991;88:1121–1127.

    PubMed  CAS  Google Scholar 

  61. Modur V, Feldhaus MJ, Weyrich AS, Jicha DL, Prescott SM, Zimmerman GA, McIntyre TM. Oncostatin M is a proinflammatory mediator. In vivo effects correlate with endothelial cell expression of inflammatory cytokines and adhesion molecules. J Clin Invest 1997;100:158–168.

    PubMed  CAS  Google Scholar 

  62. Bernard C, Merval R, Lebret M, Delerive P, Dusanter-Fourt I, Lehoux S, Créminon C, Staels B, Maclouf J, Tedgui A. Activation of human vascular smooth muscle cells by oncostatin M. Circ Res. 1998;(in press)

    Google Scholar 

  63. Moreau M, Brocheriou I, Petit L, Ninio E, Chapman MJ, Rouis M. Interleukin-8 mediates downregulation of TIMP-1 expression in cholesterol-loaded human macrophages: relevance to the stability of the atherosclerotic plaque. Circulation. 1998;(in press).

    Google Scholar 

  64. Uyemura K, Demer LL, Castle SC, Jullien D, Berliner JA, Gately MK, Warrier RR, Pham N, Fogelman AM, Modlin RL. Cross-regulatory roles of interleukin (IL)-12 and IL-10 in atherosclerosis. J Clin Invest. 1996;97:2130–2138.

    PubMed  CAS  Google Scholar 

  65. Libby P, Galis ZS. Cytokines regulate genes involved in atherogenesis. Ann N Y Acad Sci. 1995;748:158–168.

    PubMed  CAS  Google Scholar 

  66. Libby P, Sukhova G, Lee RT, Galis ZS. Cytokines regulate vascular functions related to stability of the atherosclerotic plaque. J Cardiovasc Pharmacol. 1995;25(Suppl 2):S9–S12.

    PubMed  CAS  Google Scholar 

  67. Gupta S, Pablo AM, Jiang Xc, Wang N, Tall AR, Schindler C. IFN-γ potentiates atherosclerosis in ApoE knock-out mice. J Clin Invest. 1997;99:2752–2761.

    PubMed  CAS  Google Scholar 

  68. LeBoeuf RC, Schreyer SA. The role of tumor necrosis factor-α receptors in atherosclerosis. Trends Cardiovasc Med. 1998;8:131–138.

    CAS  Google Scholar 

  69. van Lenten BJ, Fogelman AM. Lipopolysaccharide-induced inhibition of scavenger receptor expression in human monocyte-macrophages is mediated through tumor necrosis factor-α. J Immunol. 1992;148:112–116.

    PubMed  Google Scholar 

  70. Hsu HY, Nicholson AC, Hajjar DP. Inhibition of macrophage scavenger receptor activity by tumor necrosis factor-α is transcriptionally and post-transcriptionally regulated. J Biol Chem. 1996;271:7767–7773.

    PubMed  CAS  Google Scholar 

  71. Elhage R, Maret A, Pieraggi MT, Thiers JC, Arnal JF, Bayard F. Differential effects of interleukin-1 receptor antagonist and tumor necrosis factor binding protein on fatty-streak formation in apolipoprotein E-deficient mice. Circulation. 1998;97:242–244.

    PubMed  CAS  Google Scholar 

  72. Mach F, Schonbeck U, Sukhova GK, Bourcier T, Bonnefoy JY, Pober JS, Libby P. Functional CD40 ligand is expressed on human vascular endothelial cells, smooth muscle cells, and macrophages: implications for CD40-CD40 ligand signaling in atherosclerosis. Proc Natl Acad Sci U SA. 1997;94:1931–1936.

    CAS  Google Scholar 

  73. Mach F, Schonbeck U, Sukhova GK, Atkinson E, Libby P. Reduction of atherosclerosis in mice by inhibition of CD40 signalling. Nature. 1998;394:200–203.

    PubMed  CAS  Google Scholar 

  74. Pomerantz KB, Hajjar DP, Levi R, Gross SS. Cholesterol enrichment of arterial smooth muscle cells upregulates cytokine-induced nitric oxide synthesis. Biochem Biophys Res Comm. 1993;191:103–109.

    PubMed  CAS  Google Scholar 

  75. Verbeuren TJ, Bonhomme E, Laubie M, Simonet S. Evidence for induction of nonendothelial NO synthase in aortas of cholesterol-fed rabbits. J Cardiovasc Pharmacol. 1993;21:841–845.

    PubMed  CAS  Google Scholar 

  76. Buttery LD, Springall DR, Chester AH, Evans TJ, Standfield EN, Parums DV, Yacoub MH, Polak JM. Inducible nitric oxide synthase is present within human atherosclerotic lesions and promotes the formation and activity of peroxynitrite. Lab Invest. 1996;75:77–85.

    PubMed  CAS  Google Scholar 

  77. Mallat Z, Heymes C, Ohan J, Lesèche G, Tedgui A. Expression of Interleukin-10 in advanced human atherosclerotic plaques. Relation to inducible nitric oxide synthase and cell death. Arterioscler Thromb Vase Biol. 1998;(in press)

    Google Scholar 

  78. Geng YJ, Wu Q, Muszynski M, Hansson GK, Libby P. Apoptosis of vascular smooth muscle cells induced by in vitro stimulation with interferon-γ, tumor necrosis factor-α, and interleukin-1 β. Arterioscler Thromb Vasc Biol. 1996;16:19–27.

    PubMed  CAS  Google Scholar 

  79. Albina JE, Cui SJ, Mateo RB, Reichner JS. Nitric-oxide-mediated apoptosis in murine peritoneal macrophages. J Immunol. 1993, 150:5080–5085.

    PubMed  CAS  Google Scholar 

  80. Kockx MM, Muhring J, Knaapen MW, de Meyer GR. RNA synthesis and splicing interferes with DNA in situ end labeling techniques used to detect apoptosis. Am J Pathol. 1998;152:885–888

    PubMed  CAS  Google Scholar 

  81. Luoma JS, Stralin P, Marklund SL, Hiltunen TP, Sarkioja T, Yla-Herttuala S. Expression of extracellular SOD and iNOS in macrophages and smooth muscle cells in human and rabbit atherosclerotic lesions: colocalization with epitopes characteristic of oxidized LDL and peroxynitrite-modified proteins. Arterioscler Thromb Vasc Biol. 1998;18:157–167.

    PubMed  CAS  Google Scholar 

  82. Szabo C. DNA strand breakage and activation of poly-ADP ribosyltransferase: a cytotoxic pathway triggered by peroxynitrite. Free Radic Biol Med. 1996;21:855–869.

    PubMed  CAS  Google Scholar 

  83. de Vries JE. Immunosuppressive and anti-inflammatory properties of interleukin 10. Ann Med. 1995;27:537–541.

    PubMed  Google Scholar 

  84. de Waal Malefyt R, Abrams RJ, Bennett B, Figdor CG, de Vries JE. Interleukin-10 (IL-10) inhibits cytokine synthesis by human monocytes-an autoregulatory role of IL-10 produced by monocytes. J Exp Med. 1991;174:1209–1220.

    PubMed  Google Scholar 

  85. Gérard C, Bruyns C, Marchant A, Abramowicz D, Vandebeele P, Delvaux A, Fiers W, Goldman M, Velu T. Interleukin-10 reduces the release of tumor necrosis factor and prevents lethality in experimental endotoxemia. J Exp Med. 1993;177:547–550.

    PubMed  Google Scholar 

  86. Arai T, Hiromatsu K, Nishimura H, Kimura Y, Kobayashi N, Ishida H, Nimura Y, Yoshikai Y. Endogenous interleukin 10 prevents apoptosis in macrophages during salmonella infection. Biochem Biophys Res Commun. 1995;213:600–607.

    PubMed  CAS  Google Scholar 

  87. Cohen SB, Crawley JB, Kahan MC, Feldmann M, Foxwell BM. Interleukin-10 rescues T cells from apoptotic cell death: association with an upregulation of Bcl-2. Immunology. 1997;92:1–5.

    PubMed  CAS  Google Scholar 

  88. Pober JS, Cotran RS. The role of endothelial cells in inflammation. Transplantation. 1990, 50:537–544.

    PubMed  CAS  Google Scholar 

  89. Li H, Cybulsky MI, Gimbrone Jr MA, Libby P. An atherogenic diet rapidly induces VCAM-1, a cytokine-regulatable mononuclear leukocyte adhesion molecule, in rabbit aortic endothelium. Arterioscler Thromb. 1993;13:197–204.

    PubMed  Google Scholar 

  90. O’Brien KD, Allen MD, McDonald TO, Chait A, Harlan JM, Fishbein D, McCarty J, Ferguson M, Hudkins K, Benjamin CD, Lobb R, Alpers CE. Vascular cell adhesion molecule-1 is expressed in human coronary atherosclerotic plaques. Implications for the mode of progression of advanced coronary atherosclerosis. J Clin Invest. 1993;92:945–951.

    PubMed  CAS  Google Scholar 

  91. Hla T, Neilson K. Human cyclooxygenase-2 cDNA. Proc Natl Acad Sci USA, 1992;89:7384–7388.

    PubMed  CAS  Google Scholar 

  92. Yoshizumi M, Perrella MA, Burnett JC Jr, Lee ME. Tumor necrosis factor downregulates an endothelial nitric oxide synthase mRNAby shortening its half-life. Circ Res. 1993;73:205–209.

    PubMed  CAS  Google Scholar 

  93. Raines E, Dower S, Ross R.. Interleukin-1 mitogenic activity for fibroblast and smooth muscle cells is due to PDGF-AA. Science. 1989;243:393–396.

    PubMed  CAS  Google Scholar 

  94. Galis Z, Muszynski M, Sukhova G, Simon-Morrissey E, Unemori EN, Lark MW, Amento E, P Libby. Cytokine-stimulated human vascular smooth cells synthesize a complement of enzymes required for extracellular matrix digestion. Circ Res. 1994;75:181–189.

    PubMed  CAS  Google Scholar 

  95. Fabunmi RP, Sukhova GK, Sugiyama S, Libby P. Expression of Tissue Inhibitor of Matalloproteinases-3 in human atheroma and regulation in lesion-associated cells. Circ Res. 1998;83:270–278.

    PubMed  CAS  Google Scholar 

  96. Hughes DA, Townsend PJ, Haslam PL. Enhancement of the antigen-presenting function of monocytes by cholesterol: possible relevance to inflammatory mechanisms in extrinsic allergic alveolitis and atherosclerosis. Clin Exp Immunol. 1992;87:279–286.

    PubMed  CAS  Google Scholar 

  97. Frostegard J, Wu R, Giscombe R, Holm G, Lefvert AK, Nilsson J. Induction of T-cell activation by oxidized low density lipoprotein. Arterioscler Thromb. 1992;12:461–467.

    PubMed  CAS  Google Scholar 

  98. Liao F, Berliner JA, Mehrabian M, Navab M, Demer LL, Lusis AJ, Fogelman AM. Minimally modified low density lipoprotein is biologically active in vivo in mice. J Clin Invest. 1991;87:2253–2257.

    PubMed  CAS  Google Scholar 

  99. Liao F, Andalabi A, deBeer FC, Fogelman AM, Lusis AJ. Genetic control of inflammatory gene induction and NF-kB-like transcription factor activation in response to an etherogenic diet in mice. J Clin Invest. 1993;91:2572–2579.

    PubMed  CAS  Google Scholar 

  100. Fong LG, Fong TAT, Copper AD. Inhibition of lipopolysaccharide-induced interleukin-lβ mRNA expression in mouse macrophages by oxidized low density lipoprotein. J Lipid Res. 1991;32:1899–1910.

    PubMed  CAS  Google Scholar 

  101. Salonen JT, Yla-Herttuala S, Yamamoto R, Butler S, Korpela H, Salonen R, Nyyssonen K, Palinski W, Witztum JL. Autoantibodies against oxydised LDL and progression of carotid atherosclerosis. Lancet. 1992;339:883–887.

    PubMed  CAS  Google Scholar 

  102. Glagov S, Weisenberg E, Zarins CK, Stankunavicius R, Kolettis GJ. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med. 1987;316:1371–1375.

    PubMed  CAS  Google Scholar 

  103. McPherson DD, Sirna SJ, Hiratza LF, Thorpe LJ, Armstrong ML, Marcus ML, Kerber RE. Coronary arterial remodeling studied by high-frequency epicardial echocardiography: an early compensatory mechanism in patients with obstructive coronary atherosclerosis. J Am Coll Cardiol. 1991;17:79–86.

    PubMed  CAS  Google Scholar 

  104. McPherson DD, Johson MR, Alvarez NM, Rewcastle NB, Collins SM, Armstrong ML, Kieso RA, Thorpe LJ, Marcus ML, Kerber RE. Variable morphology of coronary atherosclerosis: characterization of atherosclerotic plaque and residual arterial lumen size and shape by epicardial echocardiography. J Am Coll Cardiol. 1992;19:593–599.

    PubMed  CAS  Google Scholar 

  105. Clarkson TB, Prichard RW, Morgan TM, Petrick GS, Klein KP. Remodeling of coronary arteries in human and nonhuman primates. JAMA. 1994;271:289–294.

    PubMed  CAS  Google Scholar 

  106. Steinke W, Els T, Hennerici M. Compensatory carotid artery dilatation in early atherosclerosis. Circulation. 1994;89:2578–2581.

    PubMed  CAS  Google Scholar 

  107. Losordo DW, Rosenfield K, Kaufman J, Pieczek A, Isner JM. Focal compensatory enlargement of human arteries in response to progressive atherosclerosis. In vivo documentation using intravascular ultrasound. Circulation. 1994;89:2570–2577.

    PubMed  CAS  Google Scholar 

  108. Davies MJ, Thomas AC. Plaque fissuring: the cause of acute myocardial infarction, sudden ischemic death, and cescendo angina. Br Heart J. 1985;53:363–373.

    PubMed  CAS  Google Scholar 

  109. Fuster V, Badimon I, Badimon J, Chesebro J. The pathogenesis of coronary artery disease and the acute coronary syndromes. N Engl J Med. 1992;326:242–250.

    PubMed  CAS  Google Scholar 

  110. Richardson PD, Davies MJ, Born GV. Influence of plaque configuration and stress distribution on fissuring of coronary atherosclerotic plaques. Lancet. 1989;2:941–944.

    PubMed  CAS  Google Scholar 

  111. Lee RT, Libby P. The unstable atheroma. Arterioscler Thromb Vasc Biol. 1997;17:1859–1867.

    PubMed  CAS  Google Scholar 

  112. Kaplan M, Aviram M. Oxidized LDL binding to a macrophage-secreted extracellular matrix. Biochem Biophys Res Commun. 1997;237:271–276.

    PubMed  CAS  Google Scholar 

  113. Weissberg PL, Clesham GJ, Bennett MR. Is vascular smooth muscle cell proliferation beneficial? Lancet. 1996;347:305–307.

    PubMed  CAS  Google Scholar 

  114. Henney AM, Wakeley PR, Davies MJ, Foster K, Hembry R, Murphy G, Humphries S. Localization of stromelysin gene expression in atherosclerotic plaques by in situ hybridization. Proc Natl Acad Sci U S A 1991;88:8154–8158.

    PubMed  CAS  Google Scholar 

  115. Galis ZS, Sukhova GK, Lark MW, Libby P. Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest. 1994;94:2493–2503.

    PubMed  CAS  Google Scholar 

  116. Nikkari ST, Geary RL, Hatsukami T, Ferguson M, Forough R, Alpers CE, Clowes AW. Expression of collagen, interstitial collagenase, and tissue inhibitor of metalloproteinases-1 in restenosis after carotid endarterectomy. Am J Pathol. 1996;148:777–783.

    PubMed  CAS  Google Scholar 

  117. Halpert I, Sires UI, Roby JD, Potter-Perigo S, Wight TN, Shapiro SD, Welgus HG, Wicklirie SA, Parks WC. Matrilysin is expressed by lipid-laden macrophages at sites of potential rupture in atherosclerotic lesions and localizes to areas of versican deposition, a proteoglycan substrate for the enzyme. Proc Natl Acad Sci U S A. 1996, 93:9748–9753.

    PubMed  CAS  Google Scholar 

  118. van der Wal AC, Becker AE, Das PK. Medial thinning and atherosclerosis-evidence for involvement of a local inflammatory effect. Atherosclerosis. 1993;103:55–64.

    PubMed  Google Scholar 

  119. Joris I, Zand T, Nunnari JJ, Krolikowsk FJ, Majno G. Studies on the pathogenesis of atherosclerosis. 1. Adhesion and emigration of mononuclear cells in the aorta of hypercholesterolemic rats. Am J Pathol. 1983;113:341–358.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Kluwer Academic Publishers

About this chapter

Cite this chapter

Tedgui, A., Bernard, C., Mallat, Z. (1999). Pathobiology of Atherosclerosis. In: Levy, B.I., Tedgui, A. (eds) Biology of the Arterial Wall. Basic Science for the Cardiologist, vol 1. Springer, Boston, MA. https://doi.org/10.1007/978-0-585-38146-6_12

Download citation

  • DOI: https://doi.org/10.1007/978-0-585-38146-6_12

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-7923-8458-8

  • Online ISBN: 978-0-585-38146-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics