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Special Communication |

Hemodynamic Shear Stress and Its Role in Atherosclerosis

Adel M. Malek, MD, PhD; Seth L. Alper, MD, PhD; Seigo Izumo, MD
JAMA. 1999;282(21):2035-2042. doi:10.1001/jama.282.21.2035.
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Atherosclerosis, the leading cause of death in the developed world and nearly the leading cause in the developing world, is associated with systemic risk factors including hypertension, smoking, hyperlipidemia, and diabetes mellitus, among others. Nonetheless, atherosclerosis remains a geometrically focal disease, preferentially affecting the outer edges of vessel bifurcations. In these predisposed areas, hemodynamic shear stress, the frictional force acting on the endothelial cell surface as a result of blood flow, is weaker than in protected regions. Studies have identified hemodynamic shear stress as an important determinant of endothelial function and phenotype. Arterial-level shear stress (>15 dyne/cm2) induces endothelial quiescence and an atheroprotective gene expression profile, while low shear stress (<4 dyne/cm2), which is prevalent at atherosclerosis-prone sites, stimulates an atherogenic phenotype. The functional regulation of the endothelium by local hemodynamic shear stress provides a model for understanding the focal propensity of atherosclerosis in the setting of systemic factors and may help guide future therapeutic strategies.

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Figure 1. Hemodynamic Shear Stress
Graphic Jump Location
A, Cross-sectional schematic diagram of a blood vessel illustrating hemodynamic shear stress, τs, the frictional force per unit area acting on the inner vessel wall and on the luminal surface of the endothelium as a result of the flow of viscous blood. B,Tabular diagram illustrating the range of shear stress magnitudes encountered in veins, arteries, and in low-shear and high-shear pathologic states.
Figure 2. Localization of Atherosclerosis Lesions
Graphic Jump Location
A, Schematic illustration of the focal nature of atherosclerosis and its tendency to involve the outer walls of vascular bifurcations such as the carotid, coronary, renal, and iliac artery flow dividers. B, Left lateral cervical carotid arteriogram in a 75-year-old man who experienced an embolic stroke in the left temporal lobe. Focal narrowing is seen at the outer walls of the common carotid artery bifurcation in both the internal carotid artery (arrowhead) and the external carotid artery (arrowhead). C, Velocity map of the carotid bifurcation at end-systole using computational fluid dynamic modeling illustrates the lower velocities seen at the outer lateral edges (blue).38 The computed wall shear stress (bottom) shows the focal low shear magnitude at the outer walls that correspond exactly to the atherosclerosis-prone areas of the carotid bifurcation (compare with B) and is in contrast with the less susceptible inner regions of the bifurcation where flow velocity and, consequently, hemodynamic shear stress at the vessel wall is higher (yellow and green). (Courtesy of Drs David Saloner and Liang-Der Jou, University of California, Berkeley).
Figure 3. Transformation of Endothelial Cell Morphology by Fluid Shear Stress
Graphic Jump Location
Bovine aortic endothelial cells exposed to physiologic shear stress (>15 dyne/cm2, left panel) for 24 hours align in the direction of blood flow while those exposed to low shear stress (right panel) do not (phase contrast; original magnification ×125). See "Biological Response of the Endothelium to Shear Stress" section.
Figure 4. Model of Atherogenesis
Graphic Jump Location
Illustration of the arterial endothelial phenotypic switch from atheroprotective (left panel) to atherogenic (right panel) induced by the local low-magnitude shear stress (<4 dyne/cm2) conditions found in atherosclerosis-prone regions of vascular bifurcations.5,22,24 The atherogenic endothelial phenotype resulting from weak local hemodynamic shear stress at the vessel wall includes the low shear-mediated recruitment and activation of monocytes, increased platelet activation, increased vasoconstriction and paracrine growth stimulation of vessel wall constituents, increased oxidant state, and increased apoptosis and cellular turnover (right panel). τs Indicates shear stress; NO, nitric oxide; EC, endothelial cell; and NOS, endothelial nitric oxide sythase. For other abbreviations, see footnote to Table 1.



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