Netherlands Heart Journal

, Volume 16, Issue 8, pp 280–283 | Cite as

High shear stress influences plaque vulnerability

  • H. C. Groen
  • F. J. H. Gijsen
  • A. van der Lugt
  • M. S. Ferguson
  • T. S. Hatsukami
  • C. Yuan
  • A. F. W. van der Steen
  • J. J. Wentzel
Interuniversity Cardiology Institute of the Netherlands

shear stressplaque vulnerability

Cerebrovascular events are frequently caused by rupture of a vulnerable plaque in the carotid arteries. Rupture-prone, or vulnerable, plaques are characterised by their specific morphology and composition: a large lipid pool covered by a thin fibrous cap infiltrated by macrophages, 1 and expansive remodelling. 2,3 The strength of the cap of a vulnerable plaque is determined by the balance between cap-consolidating matrix synthesis by smooth muscle cells (SMC) and enzymatic matrix degradation induced by macrophages. 4 Studies on the spatial distribution of plaque components showed that the concentration of macrophages is higher, 5,6 the density of SMC is lower and metalloproteinase (MMP-9) activity is higher at the upstream side of the plaque compared with the downstream side, 6suggesting that plaque vulnerability is associated with the direction of the flow. Indeed, plaque rupture was observed to occur most frequently at the upstream part of a lumen...
magnetic resonance imaging 


  1. 1.
    Moreno P, Falk E, Palacios I, et al. Macrophage infiltration in acute coronary syndromes. Implications for plaque rupture. Circulation 1994;90:775-8.Google Scholar
  2. 2.
    Pasterkamp G, Schoneveld AH, van der Wal AC, et al. Relation of arterial geometry to luminal narrowing and histologic markers for plaque vulnerability: the remodeling paradox. J Am Coll Cardiol 1998/9;32:655-62.Google Scholar
  3. 3.
    Burke AP, Farb A, Malcom GT, et al. Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. N Engl J Med 1997;336:1276-82.Google Scholar
  4. 4.
    Libby P, Geng YJ, Aikawa M, et al. Macrophages and atherosclerotic plaque stability. Curr Opin Lipidol 1996;7:330-5.Google Scholar
  5. 5.
    Dirksen MT, van der Wal AC, van den Berg FM, et al. Distribution of inflammatory cells in atherosclerotic plaques relates to the direction of flow. Circulation 1998;98:2000-3.Google Scholar
  6. 6.
    Krams R, Cheng C, Helderman F, et al. Shear stress is associated with markers of plaque vulnerability and MMP-9 activity. Eurointervention. 2006;2:250-6.Google Scholar
  7. 7.
    Glagov S, Weisenberg E, Zarins CK, et al. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med 1987;316:1371-5.Google Scholar
  8. 8.
    Masawa N, Yoshida Y, Yamada T, et al. Three-dimensional analysis of human carotid atherosclerotic ulcer associated with recent thrombotic occlusion. Pathol Int 1994;44:745-52.Google Scholar
  9. 9.
    Malek AM, Alper SL, Izumo S. Hemodynamic shear stress and its role in atherosclerosis. JAMA 1999;282:2035-42.Google Scholar
  10. 10.
    Yamawaki H, Lehoux S, Berk BC. Chronic physiological shear stress inhibits tumor necrosis factor-induced proinflammatory responses in rabbit aorta perfused ex vivo. Circulation 2003;108:1619-25.Google Scholar
  11. 11.
    Ando J, Tsuboi H, Korenaga R, et al. Down-regulation of vascular adhesion molecule-1 by fluid shear stress in cultured mouse endothelial cells. Ann N Y Acad Sci 1995;748:148-56; discussionGoogle Scholar
  12. 12.
    Malek AM, Jackman R, Rosenberg RD, et al. Endothelial expression of thrombomodulin is reversibly regulated by fluid shear stress. Circ Res 1994;74:852-60.Google Scholar
  13. 13.
    Krams R, Wentzel J, Oomen J, et al. Evaluation of endothelial shear stress and 3D geometry as factors determining the development of atherosclerosis and remodeling in human coronary arteries in vivo. Combining 3D reconstruction from angiography and IVUS (ANGUS) with computational fluid dynamics. Arterioscler Thromb Vasc Biol 1997;17:2061-5.Google Scholar
  14. 14.
    Wentzel JJ, Janssen E, Vos J, et al. Extension of increased atherosclerotic wall thickness into high shear stress regions is associated with loss of compensatory remodeling. Circulation 2003;108:17-23.Google Scholar
  15. 15.
    Cheng C, Tempel D, van Haperen R, et al. Atherosclerotic lesion size and vulnerability are determined by patterns of fluid shear stress. Circulation 2006;113:2744-53.Google Scholar
  16. 16.
    Chatzizisis YS, Jonas M, Coskun AU, et al. Prediction of the Localization of High-Risk Coronary Atherosclerotic Plaques on the Basis of Low Endothelial Shear Stress. An Intravascular Ultrasound and Histopathology Natural History Study. Circulation 2008;26:993-1002.Google Scholar
  17. 17.
    Kolodgie FD, Gold HK, Burke AP, et al. Intraplaque hemorrhage and progression of coronary atheroma. N Engl J Med 2003;349:2316-25.Google Scholar
  18. 18.
    sSlager CJ, Wentzel JJ, Gijsen FJ, et al. The role of shear stress in the destabilization of vulnerable plaques and related therapeutic implications. Nat Clin Pract Cardiovasc Med 2005;2:456-64.Google Scholar
  19. 19.
    Gijsen F, Wentzel J, Mastik F, et al. Shear stress predicts distribution of high strain spots on plaques in human coronary arteries. Eur Heart J 2006;27 (Suppl I):583-3.Google Scholar
  20. 20.
    Saam T, Ferguson MS, Yarnykh VL, et al. Quantitative evaluation of carotid plaque composition by in vivo MRI. Arterioscler Thromb Vasc Biol 2005;25:234-9.Google Scholar
  21. 21.
    Schaar JA, de Korte CL, Mastik F, et al. Characterizing vulnerable plaque features with intravascular elastography. Circulation. 2003;25:2636-41.Google Scholar
  22. 22.
    Schaar JA, Regar E, Mastik F, et al. Incidence of high-strain patterns in human coronary arteries: assessment with three-dimensional intravascular palpography and correlation with clinical presentation. Circulation 2004;109:2716-9.Google Scholar

Copyright information

© Bohn Stafleu van Loghum 2008

Authors and Affiliations

  • H. C. Groen
    • 1
  • F. J. H. Gijsen
  • A. van der Lugt
  • M. S. Ferguson
  • T. S. Hatsukami
  • C. Yuan
  • A. F. W. van der Steen
  • J. J. Wentzel
  1. 1.

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