title: Atherosclerotic lesion size and vulnerability are determined by patterns of fluid shear stress.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Cardiology, Thoraxcenter, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Caroline
authors.initials: C
authors.lastname: Cheng
authors.forename: Dennie
authors.initials: D
authors.lastname: Tempel
authors.forename: Rien
authors.initials: R
authors.lastname: van Haperen
authors.forename: Arjen
authors.initials: A
authors.lastname: van der Baan
authors.forename: Frank
authors.initials: F
authors.lastname: Grosveld
authors.forename: Mat J A P
authors.initials: MJ
authors.lastname: Daemen
authors.forename: Rob
authors.initials: R
authors.lastname: Krams
authors.forename: Rini
authors.initials: R
authors.lastname: de Crom
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D001783:Blood Flow Velocity; D002097:C-Reactive Protein / Q000096:biosynthesis; D002339:Carotid Arteries / Q000737:chemistry / Q000503:physiopathology* / Q000648:ultrastructure; D016893:Carotid Stenosis / Q000473:pathology / Q000503:physiopathology*; D004036:Diet, Atherogenic; D018056:Hemorheology; D006470:Hemorrhage / Q000209:etiology; D006938:Hyperlipoproteinemia Type II / Q000150:complications / Q000209:etiology / Q000235:genetics; D006965:Hyperplasia; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008055:Lipids / Q000032:analysis; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D019736:Prostheses and Implants; D033081:Shear Strength; D013314:Stress, Mechanical; D017539:Tunica Intima / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D001057:Apolipoproteins E; D015850:Interleukin-6; D008055:Lipids; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D000804:Angiotensin II; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein