Published online before print June 5, 2006, doi: 10.1161/CIRCULATIONAHA.105.590018
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(Circulation. 2006;113:2744-2753.)
© 2006 American Heart Association, Inc.
Vascular Medicine |
Atherosclerotic Lesion Size and Vulnerability Are Determined by Patterns of Fluid Shear Stress
From the Departments of Cardiology, Thoraxcenter (C.C., D.T., A.v.d.B., R.K.), and of Cell Biology and Genetics (R.v.H., F.G., R.d.C.), Erasmus MC, University Medical Center, Rotterdam; the Department of Pathology (M.J.A.P.D.), Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht; and the Department of Vascular Surgery (R.d.C.), Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Correspondence to Rini de Crom, PhD, Department of Cell Biology and Genetics, Erasmus MC, Room Ee1073, Dr Molewaterplein 50, 3015 GD Rotterdam, The Netherlands. E-mail m.decrom{at}erasmusmc.nl
Received September 27, 2005; revision received March 16, 2006; accepted April 4, 2006.
Background— Atherosclerotic lesions are predominantly observed in curved arteries and near side branches, where low or oscillatory shear stress patterns occur, suggesting a causal connection. However, the effect of shear stress on plaque vulnerability is unknown because the lack of an appropriate in vivo model precludes cause-effect studies.
Methods and Results— We developed a perivascular shear stress modifier that induces regions of lowered, increased, and lowered/oscillatory (ie, with vortices) shear stresses in mouse carotid arteries and studied plaque formation and composition. Atherosclerotic lesions developed invariably in the regions with lowered shear stress or vortices, whereas the regions of increased shear stress were protected. Lowered shear stress lesions were larger (intima/media, 1.38±0.68 versus 0.22±0.04); contained fewer smooth muscle cells (1.9±1.6% versus 26.3±9.7%), less collagen (15.3±1.0% versus 22.2±1.0%), and more lipids (15.8±0.9% versus 10.2±0.5%); and showed more outward vascular remodeling (214±19% versus 117±9%) than did oscillatory shear stress lesions. Expression of proatherogenic inflammatory mediators and matrix metalloproteinase activity was higher in the lowered shear stress regions. Spontaneous and angiotensin II–induced intraplaque hemorrhages occurred in the lowered shear stress regions only.
Conclusions— Lowered shear stress and oscillatory shear stress are both essential conditions in plaque formation. Lowered shear stress induces larger lesions with a vulnerable plaque phenotype, whereas vortices with oscillatory shear stress induce stable lesions.
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