Abstract
Blood-flow-induced shear stress acting on the arterial wall is of paramount importance in vascular biology. Endothelial cells sense shear stress and largely control its value in a feedback-control loop by adapting the arterial dimensions to blood flow. Nevertheless, to allow for variations in arterial geometry, such as bifurcations, shear stress control is modified at certain eccentrically located sites to let it remain at near-zero levels. In the presence of risk factors for atherosclerosis, low shear stress contributes to local endothelial dysfunction and eccentric plaque build up, but normal-to-high shear stress is atheroprotective. Initially, lumen narrowing is prevented by outward vessel remodeling. Maintenance of a normal lumen and, by consequence, a normal shear stress distribution, however, prolongs local unfavorable low shear stress conditions and aggravates eccentric plaque growth. While undergoing such growth, eccentric plaques at preserved lumen locations experience increased tensile stress at their shoulders making them prone to fissuring and thrombosis. Consequent loss of the plaque-free wall by coverage with thrombus and new tissue may bring shear-stress-controlled lumen preservation to an end. This change causes shear stress to increase, which as a new condition may transform the lesion into a rupture-prone vulnerable plaque. We present a discussion of the role of shear stress, in setting the stage for the generation of rupture-prone, vulnerable plaques, and how this may be prevented.
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Special thanks to PJ de Feyter and EP McFadden, who greatly improved the readability of the paper.
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Glossary
- AMERICAN HEART ASSOCIATION TYPE IV LESION
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Plaques consisting of a dense accumulation of extracellular lipid, occupying an extensive but well-defined region of the intima
- AMERICAN HEART ASSOCIATION TYPE III LESIONS
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Seen in young adults as visible fatty-streak lesions, with layers of macrophage foam cells, minimal coarse-grained particles and pools and droplets of extracellular lipid
- SHEAR STRESS
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Force per unit area exerted by blood flow on the vessel wall that depends on blood viscosity and flow velocity profile
- MECHANICAL STRESS
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Force per unit area that balances the load applied to a body
- SHEAR RATE
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The rate at which adjacent layers of fluid move with respect to each other, or to a stationary surface, measured in reciprocal seconds (s−1, derived from ms−1/m)
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Slager, C., Wentzel, J., Gijsen, F. et al. The role of shear stress in the generation of rupture-prone vulnerable plaques. Nat Rev Cardiol 2, 401–407 (2005). https://doi.org/10.1038/ncpcardio0274
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DOI: https://doi.org/10.1038/ncpcardio0274
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