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The role of shear stress in the destabilization of vulnerable plaques and related therapeutic implications

Nature Clinical Practice Cardiovascular Medicine volume 2, pages 456–464 (2005)Cite this article

Abstract

American Heart Association type IV plaques consist of a lipid core covered by a fibrous cap, and develop at locations of eccentric low shear stress. Vascular remodeling initially preserves the lumen diameter while maintaining the low shear stress conditions that encourage plaque growth. When these plaques eventually start to intrude into the lumen, the shear stress in the area surrounding the plaque changes substantially, increasing tensile stress at the plaque shoulders and exacerbating fissuring and thrombosis. Local biologic effects induced by high shear stress can destabilize the cap, particularly on its upstream side, and turn it into a rupture-prone, vulnerable plaque. Tensile stress is the ultimate mechanical factor that precipitates rupture and atherothrombotic complications. The shear-stress-oriented view of plaque rupture has important therapeutic implications. In this review, we discuss the varying mechanobiologic mechanisms in the areas surrounding the plaque that might explain the otherwise paradoxical observations and unexpected outcomes of experimental therapies.

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Figure 1: Plaque regions for which blood-flow-related observations on plaque composition and vascular remodeling have been reported.
Figure 2: Proposed main mechanisms induced by shear stress that affect the stability of the cap of a vulnerable plaque.
Figure 3: Effects of a drop in blood pressure on global plaque morphology, and a symmetrical lesion model that allows the calculation of tensile stress.

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Acknowledgements

Special thanks to PJ de Feyter and EP McFadden, who greatly improved the readability of the paper, and to JCH Schuurbiers for useful discussion and preparing the figures.

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Authors and Affiliations

  1. Hemodynamics Laboratory of the Department of Biomedical Engineering,

    CJ Slager, JJ Wentzel, FJH Gijsen, A Thury, JA Schaar & PW Serruys

  2. Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands

    CJ Slager, JJ Wentzel, FJH Gijsen, A Thury, JA Schaar & PW Serruys

  3. Consultant Pathologist at the Academic Medical Center, Amsterdam, The Netherlands

    AC van der Wal

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Slager, C., Wentzel, J., Gijsen, F. et al. The role of shear stress in the destabilization of vulnerable plaques and related therapeutic implications. Nat Rev Cardiol 2, 456–464 (2005). https://doi.org/10.1038/ncpcardio0298

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