Skip Navigation

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Disclaimer
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Gensini, G.F.
Right arrow Articles by Dilaghi, B.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Gensini, G.F.
Right arrow Articles by Dilaghi, B.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?


The unstable plaque

G.F. Gensini* and B. Dilaghi

Department of Critical Care Medicine and Surgery, University of Florence and Azienda Ospedaliera Careggi, Florence, Italy

* Correspondence: Professor G.F. Gensini, Dipartimento di Area Critica Medico-chirurgica, University of Florence and Azienda Ospedaliera Careggi, Viale Morgagni 85, Florence, Italy.

Abstract

Acute thrombosis, which frequently complicates the evolution of atherosclerosis, leads to cardiovascular, cerebrovascular and peripheral events. Thrombosis occurs over plaques because of a disruption or tear in the cap of a lipid-rich plaque that leads to exposure of blood to highly thrombogenic plaque components because of denudation and erosion of the endothelial surface. Therefore, the crucial question is why atherosclerosis suddenly becomes complicated by life-threatening thrombosis. Plaque stabilization could be a crucial therapeutic intervention to combat the harmful consequences of coronary atherosclerosis through agents that can favourably impact on plaque pathobiology.

Key Words: Atherosclerosis • passivation • plaque

References

  1. Stary HC, Chandler AB, Dinsmore RE, et al. A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. Circulation. 1995;92:1355–1374[Abstract/Free Full Text]
  2. Zhang Y, Cliff WJ, Schoefl GI, Higgins G. Plasma protein insudation as an index of early coronary atherogenesis. Am J Pathol. 1993;143:496–506[Abstract]
  3. Johnson-Tidey RR, McGregor JL, Taylor PR, Poston RN. Increase in the adhesion molecule P-selectin in endothelium overlying atherosclerotic plaques. Am J Pathol. 1994;144:952–961[Abstract]
  4. Davies MJ, Gordon JL, Gearing AJH, Pigott R, Woolf N, Katz D, Kyriakopoulos A. The expression of the adhesion molecules ICAM-1, VCAM-1, PECAM, and E-selectin in human atherosclerosis. J Pathol. 1993;171:223–229[CrossRef][Web of Science][Medline]
  5. Faruqi RM, DiCorleto PE. Mechanisms of monocyte recruitment and accumulation. Br Heart J. 1993;69:S19–S29 (suppl)
  6. Hansson GK. Immune and inflammatory mechanisms in the development of atherosclerosis. Br Heart J. 1993;69:S38–S41 (suppl)
  7. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993;362:801–809[CrossRef][Medline]
  8. Rekhter MD, Gordon D. Does platelet-derived growth factor-A chain stimulate proliferation of arterial mesenchymal cells in human atherosclerotic plaques? Cire Res. 1994;75:410–417
  9. Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol: modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med. 1989;320:915–924[Web of Science][Medline]
  10. Ylä-Herttuala S, Rosenfeld ME, Parthasarathy S, Sigal E, Särkioja T, Witztum JL, Steinberg D. Gene expression in macrophage-rich human atherosclerotic lesions: 15-lipoxygenase and acetyl low density lipoprotein receptor messenger RNA colocalize with oxidation specific lipid-protein adducts. J Clin Invest. 1991;87:1146–1152
  11. Witztum JL. The oxidation hypothesis of atherosclerosis. Lancet. 1994;344:793–795[CrossRef][Web of Science][Medline]
  12. Demer LL, Watson KE, Boström K. Mechanism of calcification in atherosclerosis. Trends Cardiovasc Med. 1994;4:45–49[CrossRef]
  13. Berliner JA, Navab M, Fogelman AM, et al. Atherosclerosis: basic mechanisms: oxidation, inflammation, and genetics. Circulation. 1995;91:2488–2496[Abstract/Free Full Text]
  14. Fuster V, Badimon L, Badimon J, Chesebro HI. The pathogenesis of coronary artery disease and the acute coronary syndromes. N Engl J Med. 1992;326:242–250Fuster V, Badimon L, Badimon J, Chesebro HI. The pathogenesis of coronary artery disease and the acute coronary syndromes. N Engl J Med. 1992;326:310–318[Web of Science][Medline]
  15. Ambrose JA, Tannenbaum MA, Alexopoulos D, et al. Angiographic progression of coronary artery disease and the development of myocardial infarction. J Am Coll Cardiol. 1988;12:56–62[Abstract]
  16. Little WC, Constantinescu M, Applegate RJ, Kutcher MA, Burrows MT, Kahl FR, Santamore WP. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease? Circulation. 1988;78:1157–1166[Abstract/Free Full Text]
  17. Nobuyoshi M, Tanaka M, Nosaka H, et al. Progression of coronary atherosclerosis: is coronary spasm related to progression? J Am Coll Cardiol. 1991;18:904–910[Abstract]
  18. Giroud D, Li JM, Urban P, Meier B, Rutishauser W. Relation of the site of acute myocardial infarction to the most severe coronary arterial stenosis at prior angiography. Am J Cardiol. 1992;69:729–732[CrossRef][Web of Science][Medline]
  19. Alderman EL, Corley SD, Fisher LD, et al. Five-year angiographic follow-up of factors associated with progression of coronary artery disease in the Coronary Artery Surgery Study (CASS). J Am Coll Cardiol. 1993;22:1141–1154[Abstract]
  20. Danchin N. Is myocardial revascularisation for tight coronary stenoses always necessary? Lancet. 19993;342:224–225
  21. Ge J, Erbel R, Zamorano J, et al. Coronary artery remodeling in atherosclerotic disease: an intravascular ultrasound study in vivo. Coron Artery Dis. 1993;4:981–986[Web of Science][Medline]
  22. van der Wal A, Becker A, van der Loos C, Das P. 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;89:36–44[Abstract/Free Full Text]
  23. Falk E. Plaque rupture with severe pre-existing stenosis precipitating coronary thrombosis: characteristics of coronary atherosclerotic plaques underlying fatal occlusive thrombi. Br Heart J. 1983;50:127–134[Abstract/Free Full Text]
  24. Richardson PD, Davies MJ, Born GVR. Influence of plaque configuration and stress distribution on fissuring of coronary atherosclerotic plaques. Lancet. 1989;2:941–944[CrossRef][Web of Science][Medline]
  25. Frink RJ. Chronic ulcerated plaques: new insights into the pathogenesis of acute coronary disease. J Invasive Cardiol. 1994;6:173–185[Web of Science][Medline]
  26. Falk E. Morphologic features of unstable atherothrombotic plaques underlying acute coronary syndromes. Am J Cardiol. 1989;63(suppl E):114E–120E[CrossRef][Medline]
  27. Gertz SD, Roberts WC. Hemodynamic shear force in rupture of coronary arterial atherosclerotic plaques. Am J Cardiol. 1990;66:1368–1372[CrossRef][Web of Science][Medline]
  28. Davies MJ, Richardson PD, Woolf N, Katz DR, Mann J. Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, macrophage, and smooth muscle cell content. Br Heart J. 1993;69:377–381[Abstract/Free Full Text]
  29. Burleigh MC, Briggs AD, Lendon CL, Davies MJ, Born GV, Richardson PD. Collagen types I and III, collagen content, GAGS and mechanical strength of human atherosclerotic plaque caps: span-wise variations. Atherosclerosis. 1992;96:71–81[CrossRef][Web of Science][Medline]
  30. Lee RT, Grodzinsky AJ, Frank EH, Kamm RD, Schoen FJ. Structure-dependent dynamic mechanical behavior of fibrous caps from human atherosclerotic plaques. Circulation. 1991;83:1764–1770[Abstract/Free Full Text]
  31. Poston RN, Haskard DO, Coucher JR, Gall NP, Johnson-Tidey RR. Expression of intercellular adhesion molecule-1 in atherosclerotic plaques. Am J Pathol. 1992;140:665–673[Abstract]
  32. Lendon CL, Davies MJ, Born GVR, Richardson PD. Atherosclerotic plaque caps are locally weakened when macrophage density is increased. Atherosclerosis. 1991;87:87–90[CrossRef][Web of Science][Medline]
  33. Moreno PR, Falk E, Palacios IF, Newell JB, Fuster V, Fallon JT. Macrophage infiltration in acute coronary syndromes: implications for plaque rupture. Circulation. 1994;90:775–778[Abstract/Free Full Text]
  34. 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 USA. 1991. p. 8154–8158
  35. 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
  36. Rennick RE, Ling KLE, Humphries SE, Henney AM. Effect of acetyl-LDL on monocyte/macrophage expression of matrix metalloproteinases. [abstract]Atherosclerosis. 1994;109:192 (suppl)
  37. Kaartinen M, Penttilä A, Kovanen PT. Accumulation of activated mast cells in the shoulder region of human coronary atheroma, the predilection site of atheromatous rupture. Circulation. 1994;90:1669–1678[Abstract/Free Full Text]
  38. Atkinson JB, Harlan CW, Harlan GC, Virmani R. The association of mast cells and atherosclerosis: a morphologic study of early atherosclerotic lesions in young people. Hum Pathol. 1994;25:154–159[CrossRef][Web of Science][Medline]
  39. Jonasson L, Holm 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[Abstract/Free Full Text]
  40. Weiss SJ. Tissue destruction by neutrophils. N Engl J Med. 1989;320:365–376[Web of Science][Medline]
  41. Pasterkamp G, Schoneveld AH, van der Wal AC, et al. Inflammation of the atherosclerotic cap and shoulder of the plaque is a common and locally observed feature in unruptured plaques of femoral and coronary arteries. Arterioscler Thromb Vase Biol. 1999;19:54–58
  42. Fitzgerald JD. By what means might beta blockers prolong life after acute myocardial infarction? Eur Heart J. 1987;8:945–951
  43. Cheng GC, Loree HM, Kamm RD, Fishbein MC, Lee RT. Distribution of circumferential stress in ruptured and stable atherosclerotic lesions: a structural analysis with histopathological correlation. Circulation. 1993;87:1179–1187[Abstract/Free Full Text]
  44. Barger AC, Beeuwkes R, Lainey LL, Silverman KJ. Hypothesis: vasa vasorum and neovascularization of human coronary arteries: a possible role in the pathophysiology of atherosclerosis. N Engl J Med. 1984;310:175–177[Web of Science][Medline]
  45. Zhang Y, Cliff WJ, Schoefl GI, Higgins G. Immunohistochemical study of intimal microvessels in coronary atherosclerosis. Am J Pathol. 1993;143:164–172[Abstract]
  46. Barger AC, Beeuwkes R. Rupture of coronary vasa vasorum as a trigger of acute myocardial infarction. Am J Cardiol. 1990;66(suppl G):41G–43G[CrossRef][Medline]
  47. Aoki T, Ku DN. Collapse of diseased arteries with eccentric cross section. J Biomech. 1993;26:133–142[CrossRef][Web of Science][Medline]
  48. Mizushige K, Reisman M, Buchbinder M, Dittrich H, DeMaria AN. Atheroma deformation during the cardiac cycle: evaluation by intracoronary ultrasound. [abstract]Circulation. 1993;88(suppl I):I–550
  49. Maclsaac AI, Thomas JD, Topol EJ. Toward the quiescent coronary plaque. J Am Coll Cardiol. 1993;22:1228–1241[Abstract]
  50. Gould KL. Collapsing coronary stenosis: a Starling resistor. Int J Cardiol. 1982;2:39–42[CrossRef][Web of Science][Medline]
  51. Binns RL, Ku DN. Effect of stenosis on wall motion: a possible mechanism of stroke and transient ischemic attack. Arteriosclerosis. 1989;9:842–847[Abstract/Free Full Text]
  52. Loree HM, Kamm RD, Atkinson CM, Lee RT. Turbulent pressure fluctuations on surface of model vascular stenoses. Am J Physiol. 1991;261:H644–H650
  53. Lettino M, Dailey Sterling F, Badimon L, et al. Wall passivation for unstable angina. Semin Interv cardiol. 1986;1:60–66
  54. Platelet Receptor Inhibition in ischemic Syndrome Management (PRISM) Study investigators. A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina. N Engl J Med. 1998;338:1498–1505[Abstract/Free Full Text]
  55. Platelet Receptor Inhibition in ischemic Syndrome Management in Patients Limited by Unstable Signs and symptoms (PRISMPLUS) study investigators. Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Qwave myocardial infarction. N Engl J Med. 1998;338:1488–1497[Abstract/Free Full Text]
  56. The PARAGON investigators. Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary syndrome events in a Global Organization Network. International, randomized, controlled trial of lamifiban (a platelet IIb/IIIa inhibitor), heparin, or both in unstable angina. Circulation. 1998;97:2386–2395[Abstract/Free Full Text]
  57. The PURSUIT trial investigators. Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. N Engl J Med. 1998;339:436–444[Abstract/Free Full Text]
  58. Niwa S. Inhibitory effect of fluvastatin and HGM CoA reductase inhibitor on the expression of adhesion molecules on human monocyte cell life. Int J Immunopharmacol. 1996;18:669–675[CrossRef][Web of Science][Medline]
  59. Undas A, Brummel KE, Musial J, et al. Simvastatin depresses blood clotting by inhibing activation of prothrombin, factor V and factor XIII and by enhancing factor Va inactivation. Circulation. 2001;103:2248–2253[Abstract/Free Full Text]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?



This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Disclaimer
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Gensini, G.F.
Right arrow Articles by Dilaghi, B.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Gensini, G.F.
Right arrow Articles by Dilaghi, B.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?