title: Endothelial cell PECAM-1 promotes atherosclerotic lesions in areas of disturbed flow in ApoE-deficient mice.
abstract: OBJECTIVE
  Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) has recently been shown to form an essential element of a mechanosensory complex that mediates endothelial responses to fluid shear stress. The aim of this study was to determine the in vivo role of PECAM-1 in atherosclerosis.
  
  
  RESULTS
  We crossed C57BL/6 Pecam1(-/-) mice with apolipoprotein E-deficient (Apoe(-/-)) mice. On a Western diet, Pecam1(-/-)Apoe(-/-) mice showed reduced atherosclerotic lesion size compared to Apoe(-/-) mice. Striking differences were observed in the lesser curvature of the aortic arch, an area of disturbed flow, but not in the descending thoracic or abdominal aorta. Vascular cell adhesion molecule-1 (VCAM-1) expression, macrophage infiltration, and endothelial nuclear NF-kappaB were all reduced in Pecam1(-/-)Apoe(-/-) mice. Bone marrow transplantation suggested that endothelial PECAM-1 is the main determinant of atherosclerosis in the aortic arch, but that hematopoietic PECAM-1 promotes lesions in the abdominal aorta. In vitro data show that siRNA-based knockdown of PECAM-1 attenuates endothelial NF-kappaB activity and VCAM-1 expression under conditions of atheroprone flow.
  
  
  CONCLUSIONS
  These results indicate that endothelial PECAM-1 contributes to atherosclerotic lesion formation in regions of disturbed flow by regulating NF-kappaB-mediated gene expression.
authors.affiliation: Departments of Biomedical Engineering, Robert M Berne Cardiovascular Research Center, University of Virginia, Charlottesville, USA.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Harry
authors.forename: John M
authors.initials: JM
authors.lastname: Sanders
authors.forename: Ryan E
authors.initials: RE
authors.lastname: Feaver
authors.forename: Melissa
authors.initials: M
authors.lastname: Lansey
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Deem
authors.forename: Alexander
authors.initials: A
authors.lastname: Zarbock
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Bruce
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Pryor
authors.forename: Bradley D
authors.initials: BD
authors.lastname: Gelfand
authors.forename: Brett R
authors.initials: BR
authors.lastname: Blackman
authors.forename: Martin A
authors.initials: MA
authors.lastname: Schwartz
authors.forename: Klaus
authors.initials: K
authors.lastname: Ley
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D004041:Dietary Fats; D004195:Disease Models, Animal; D018450:Disease Progression; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D012039:Regional Blood Flow; D013314:Stress, Mechanical; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D004041:Dietary Fats; D016328:NF-kappa B; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D034741:RNA, Small Interfering; D019010:Vascular Cell Adhesion Molecule-1