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Pathogenesis of Atherosclerosis

  • Chapter
Contemporary Concepts in Cardiology

Part of the book series: Developments in Cardiovascular Medicine ((DICM,volume 217))

Abstract

Atherosclerosis is the result of a complex interaction between blood elements, disturbed flow, and vessel wall abnormality. In the prevalent view, atherosclerosis is considered a specialized type of chronic, inflammatory, fibroproliferative response of the arterial wall to various sources of injury.1 Several pathologic processes are involved in atherosclerotic plaque evolution: chronic endothelial injury, with increased permeability, endothelial activation, and monocyte recruitment; cellular growth, with smooth muscle cell migration, proliferation, and extracellular matrix synthesis; degeneration, with lipid accumulation, necrosis, and calcification; inflammation, with leukocyte activation and extracellular matrix degradation; and thrombosis, with platelet recruitment and fibrin formation. In addition, biologic processes may be involved in lesion stabilization or even regression. This chapter will review pivotal cellular and mollecular events in the processes of initiation, progression, stabilization and regression of atherosclerotic lesions.

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References

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

    Article  PubMed  CAS  Google Scholar 

  2. Seiler C, et al. Influence of serum cholesterol and other coronary risk factors on vasomotion of angiographically normal coronary arteries. Circulation, 1993: 88: 2139.

    Article  PubMed  CAS  Google Scholar 

  3. Mangin EL Jr, et al. Effects of lysolipids and oxidatively modified low density lipoprotein on endothelium-dependent relaxation of rabbit aorta. Cir Res, 1993: 72: 161.

    Article  CAS  Google Scholar 

  4. Ohara Y, Peterson TE, Harrison DG: Hypercholesterolemia increases endothelial superoxide anion production. J Clin Invest, 1993: 91: 2546.

    Article  PubMed  CAS  Google Scholar 

  5. Anderson TJ, et al. The effect of cholesterol-lowering and antioxidant therapy on endothelium-dependent coronary vasomotion. N Eng J Med, 1995: 332: 488.

    Article  CAS  Google Scholar 

  6. Gibson CM, et al. Relation of vessel wall shear stress to atherosclerosis progression in human coronary arteries. Atherosc Thromb, 1993: 13: 310.

    Article  CAS  Google Scholar 

  7. Levesque MJ, et al. Correlation of endothelial cell shape and wall shear stress in a stenosed dog aorta. Arteriosclerosis, 1986: 6: 220.

    Article  PubMed  CAS  Google Scholar 

  8. Goldstein JL, Brown MS: The low density lipoprotein pathway and its relation to atherosclerosis. Annu Rev Biochem, 1977 46: 897.

    Article  PubMed  CAS  Google Scholar 

  9. Goldstein JL, et al. Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition. Proc Natl Acad Sci USA, 1979: 76: 333.

    Article  PubMed  CAS  Google Scholar 

  10. Steinbrecher UP, et al. Modification of low density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids. Proc Natl Acad Sci USA, 1984: 83: 3883.

    Article  Google Scholar 

  11. Camejo G, et al. Identification of apoB-100 segments mediating the interaction of low-density lipoproteins with arterial proteoglycans. Arteriosclerosis, 1988: 8: 368.

    Article  PubMed  CAS  Google Scholar 

  12. Guyton JR, Klemp KF. Development of the atherosclerotic core region: chemical and ultra-structural analysis of microdissected atherosclerotic lesions from human aorta. Arterioscler Thromb, 1994: 14: 1305.

    Article  PubMed  CAS  Google Scholar 

  13. Valente AJ, et al. Mechanism in intimal monocyte-macrophage recruitment, a special role for monocyte chemotactic protein-1. Circulation, 1992: 86: III20

    PubMed  CAS  Google Scholar 

  14. Kim JA, et al. Partial characterization of leukocyte binding molecules on endothelial cells induced by minimally oxidized LDL. Arterio Thromb, 1994: 24: 427.

    Article  Google Scholar 

  15. Schwartz SM, deBlois D, O’Brien ERM. The intima: soil for atherosclerosis and restenosis. Circulation Res, 1995: 77: 445.

    Article  PubMed  CAS  Google Scholar 

  16. Bennett MR, Evan GI, Schwartz SM. Apoptosis of human vascualr smooth muscle cells derived fron normal vessels and coronary atherosclerotic plaques. J Clin Invest, 1995: 95: 2266.

    Article  PubMed  CAS  Google Scholar 

  17. Majesky MW. Smooth muscle cell subtypes: a lineage model. Restenosis Summit VII. The Cleveland Clinic Fundation, 1995: 176.

    Google Scholar 

  18. Sporn MB, et al. Some recent advances in the chemistry and biology of transforming growth factor-beta. J Cell Biol, 1987: 105: 1039.

    Article  PubMed  CAS  Google Scholar 

  19. Ross R: Atherosclerosis: a problem of the biology of the arterial wall cells and their interactions with blood components. Atherosclerosis, 1981: 1: 293.

    CAS  Google Scholar 

  20. Flugelman MY, et al. Smooth muscle cell abundance and fibroblast growth factors in coronary lesions of patients with nonfatal unstable angina: a clue to the mechanism of transformation from the stable to the unstable clinical state. Circulation, 1993: 88: 2493.

    Article  PubMed  CAS  Google Scholar 

  21. Lundberg B. Chemical composition and physical state of lipids deposits in atherosclerosis. Atherosclerosis, 1985: 56: 93.

    Article  PubMed  CAS  Google Scholar 

  22. Witztum JL. The oxidation hypothesis in atherosclerosis. Lancet, 1994; 344: 793.

    Article  PubMed  CAS  Google Scholar 

  23. Wight TN. The cell biology of arterial proteoglycans. Arteriosclerosis, 1989: 9: 1.

    Article  PubMed  CAS  Google Scholar 

  24. Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation, 1995: 92: 657.

    Article  PubMed  CAS  Google Scholar 

  25. Kragel AH, et al. Morphometric analysis of the composition of atherosclerotic plaques in the four major epicardial coronaries in acute myocardial infarction and sudden coronary death. Circulation, 1989: 80: 1747.

    Article  PubMed  CAS  Google Scholar 

  26. Fernández-Ortiz A, et al. Characterization of the relative thrombogenicity of atherosclerotic plaque components: Implications for consequences of plaque rupture. J Am Coll Cardiol, 1994: 23: 1562.

    Article  PubMed  Google Scholar 

  27. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Natural history of aortic and coronary atherosclerotic lesions in youth: findings from the PDAY study. Arterioscler Thromb, 1993: 13: 1291.

    Article  Google Scholar 

  28. Devries S, et al. Influence of age and gender on the presence of coronary calcium detected by ultrafast computed tomography. J Am Coll Cardiol, 1995: 25: 76.

    Article  PubMed  CAS  Google Scholar 

  29. Fuster V. Lewis A Conner Memorial Lecture. Mechanisms leading to myocardial infarction: Insights from studies of vascular biology. Circulation, 1994: 90: 2126.

    Article  PubMed  CAS  Google Scholar 

  30. Gertz SD, Roberts WC. Hemodynamic shear force in rupture of coronary arterial atherosclerotic plaques. Am J Cardiol, 1990: 66: 1368.

    Article  PubMed  CAS  Google Scholar 

  31. Richardson RD, Davies MJ, Born GVR: Influence of plaque configuration and stress distribution on fissuring of coronary atherosclerotic plaques. Lancet, 1989: 2: 941.

    Article  PubMed  CAS  Google Scholar 

  32. Small DM. Progression and regression of atherosclerotic lesions: insights from lipid physical biochemistry. Arteriosclerosis, 1988: 8: 103.

    Article  PubMed  CAS  Google Scholar 

  33. Loree HM, et al. Mechanical properties of model atherosclerotic lesion lipid pools. Arterioscler Thromb, 1994: 14: 230.

    Article  PubMed  CAS  Google Scholar 

  34. van der Wall AC, et al. Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology, Circulation, 1994: 89: 36.

    Article  Google Scholar 

  35. Galis ZS, et al. Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest, 1994: 94: 2493.

    Article  PubMed  CAS  Google Scholar 

  36. Shah PK, et al. Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques. Potential role of metrix-degrading metalloproteinases and implications fros plaque rupture. Circulation, 1995: 92: 1565.

    PubMed  CAS  Google Scholar 

  37. Kaartinen M, Penttild A, Kovanen PT. Accumulation of activated mast cells in the shoulder region of human coronary atheroma, the predilection site of atheromatous rupture. Circulation, 1994: 90: 1669.

    Article  PubMed  CAS  Google Scholar 

  38. MacIsaac AI, Thomas JD, Topol EJ. Toward the quiescent coronary plaque. J Am Coll Cardiol, 1993: 22: 1228.

    Article  PubMed  CAS  Google Scholar 

  39. Lee RT, Kamm RD. Vascular mechanism for the cardiologist. J Am Coll Cradiol, 1994: 23: 1289.

    Article  CAS  Google Scholar 

  40. Richardson RD, Davies MJ, Born GVR. Influence of plaque configuration and stress distribution on fissuring of coronary atherosclerotic plaques. Lancet, 1989: 2: 941.

    Article  PubMed  CAS  Google Scholar 

  41. Aoki T, Ku DN. Collapse of diseased arteries with eccentric cross section. J Biomech, 1993: 26: 133.

    Article  PubMed  CAS  Google Scholar 

  42. Alfonso F, et al. Determinats of coronary compliance in patients with coronary artery disease: an intravascular ultrasound study. J Am Coll Cardiol, 1994: 23: 879.

    Article  PubMed  CAS  Google Scholar 

  43. Fuster V, et al. The pathogenesis of coronary artery disease and the acute coronary syndromes (part I and II). N Eng J Med, 1992: 326: 242 and 310.

    Google Scholar 

  44. Wilcox JN. Thrombotic mechanisms in atherosclerosis. Cor Art Dis, 1994: 5: 223.

    Article  CAS  Google Scholar 

  45. Taubman MB. Tissue factor regulation in vascualr smooth muscle: a summary of studies performed using in vivo and in vitro models. Am J Cardiol, 1993: 72: 55C

    Article  PubMed  CAS  Google Scholar 

  46. Mailhac A, et al. Effect of an eccentric severe stenosis on fibri(ogen) deposition on severily damaged vessel wall in arterial thrombosis. Relative contribution of fibri(ogen) and platelets. Circulation, 1994: 90: 988.

    Article  PubMed  CAS  Google Scholar 

  47. Meade TW, et al. Haemostatic function and cardiovascular death: early results of a prospective study. Lancet, 1980: 1: 1050.

    Article  PubMed  CAS  Google Scholar 

  48. Rosengren A, et al. Social influences and cardiovascular risk factor as determinat of plasma fibrinogen concentration in a general population sample of middle age men. BMJ, 1990: 330: 634.

    Article  Google Scholar 

  49. Stary HC. Composition and classification of human atherosclerotic lesions. Virchows Archiv A Pathol Anat, 1992: 421: 277.

    Article  CAS  Google Scholar 

  50. Glagov S. Compensatory enlargement of human atherosclerotic coronary arteries. N Eng J Med, 1987: 316: 1371.

    Article  CAS  Google Scholar 

  51. Davies MJ, et al. Factors influencing the presence or absence of acute coronary artery thrombi in sudden ischaemic death. Eur Heart J, 1989: 10: 203.

    PubMed  CAS  Google Scholar 

  52. Merickel MB, et al. Noninvasive quantitative evaluation of atherosclerotic using MRI and image analysis. Arterioscler Thromb, 1993: 13: 1180.

    Article  PubMed  CAS  Google Scholar 

  53. Toussaint JF, et al. 13C-NMR spectroscopy of human atherosclerotic lesions: relation between fatty acid saturation, cholesteryl ester content, and luminal obstruction. Arterioscler Thromb, 1994: 14: 1951.

    Article  PubMed  CAS  Google Scholar 

  54. Brown BG, et al. Lipid lowering and plaque regression: new insights into prevention of plaque disruption and clinical events in coronary disease. Circulation, 1993: 87: 1781.

    Article  PubMed  CAS  Google Scholar 

  55. Scandinavian Simvastatin Survival Study Group. Randomized trial of cholesterol lowering in 4444 patients with coronary artery disease: the Scandinavian Simvastatin Survival Study (4S). Lancet, 1994: 344: 1383.

    Google Scholar 

  56. Pfeffer MA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction: results of the Survival and Ventricular Enlargment Trial. N Eng J Med, 1992: 327: 669.

    Article  CAS  Google Scholar 

  57. The SOLVD investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractios and congestive heart failure. N Eng J Med, 1991: 325: 293.

    Article  Google Scholar 

  58. The SOLVD investigators. Effects of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Eng J Med, 1992: 327: 685.

    Article  Google Scholar 

  59. Wright RA, et al. Effects of captopril therapy on endogenous fibrinolysis in men with recent uncomplicated myocartdial infarction. J Am Coll Cardiol, 1994: 24: 67.

    Article  PubMed  CAS  Google Scholar 

  60. Reddy KG, et al. Evidence that selective endothelial dysfunction may occur in the absence of angiographic or ultrasound atherosclerosis in patients with risk factors for atherosclerosis. J Am Coll Cardiol, 1994: 23: 833.

    Article  PubMed  CAS  Google Scholar 

  61. Yusuf S, et al. Beta blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis, 1985: 27: 335.

    Article  PubMed  CAS  Google Scholar 

  62. Fuster V, et al. Aspirin as a therapeutic agent in cardiovascular disease. Circulation, 1993: 87: 659.

    Article  PubMed  CAS  Google Scholar 

  63. Simmons ML, et al. Randomized trial of a GPIIb/IIIa platelet receptor blocker in refractory unstable angina. Circulation, 1994: 89: 596.

    Article  Google Scholar 

  64. Kleiman NS, et al. Profound inhibition of platelet aggregation with monoclonal antibody 7E3Fab after thrombolytic therapy: results of the thrombolysis and angioplasty in myocardial infarction (TAMI) 8 pilot study. J Am Coll Cardiol, 1993: 22: 381.

    Article  PubMed  CAS  Google Scholar 

  65. Antman EM, for the TIMI 9A Investigators: Hirudin in acute myocardial infarction. Safety report from the thrombolysis and thrombin inhibition in myocardial infarction (TIMI) 9A trial. Circulation, 1994: 90: 1624.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Antonio Fernandez-Ortiz
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  2. Juan J. Badimon
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  3. Valentin Fuster
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© 1999 Springer Science+Business Media New York

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Fernandez-Ortiz, A., Badimon, J.J., Fuster, V. (1999). Pathogenesis of Atherosclerosis. In: Contemporary Concepts in Cardiology. Developments in Cardiovascular Medicine, vol 217. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5007-5_1

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  • DOI: https://doi.org/10.1007/978-1-4615-5007-5_1

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7274-5

  • Online ISBN: 978-1-4615-5007-5

  • eBook Packages: Springer Book Archive

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