title: Bmper inhibits endothelial expression of inflammatory adhesion molecules and protects against atherosclerosis.
abstract: OBJECTIVE
  Bone morphogenetic proteins (Bmps) are important mediators of inflammation and atherosclerosis, though their mechanism of action is not fully understood. To better understand the contribution of the Bmp signaling pathway in vascular inflammation, we investigated the role of Bmper (Bmp endothelial cell precursor-derived regulator), an extracellular Bmp modulator, in an induced in vivo model of inflammation and atherosclerosis.
  
  
  RESULTS
  We crossed apolipoprotein E-deficient (ApoE(-/-)) mice with mice missing 1 allele of Bmper (Bmper(+/-) mice used in the place of Bmper(-/-) mice that die at birth) and measured the development of atherosclerosis in mice fed a high-fat diet. Bmper haploinsufficiency in ApoE(-/-) mice (Bmper(+/-);ApoE(-/-) mice) led to a more severe phenotype compared with Bmper(+/+);ApoE(-/-) mice. Bmper(+/-);ApoE(-/-) mice also exhibited increased Bmp activity in the endothelial cells in both the greater and lesser curvatures of the aortic arch, suggesting a role for Bmper in regulating Bmp-mediated inflammation associated with laminar and oscillatory shear stress. Small interfering RNA knockdown of Bmper in human umbilical vein endothelial cells caused a dramatic increase in the inflammatory markers intracellular adhesion molecule 1 and vascular cell adhesion molecule 1 at rest and after exposure to oscillatory and laminar shear stress.
  
  
  CONCLUSIONS
  We conclude that Bmper is a critical regulator of Bmp-mediated vascular inflammation and that the fine-tuning of Bmp and Bmper levels is essential in the maintenance of normal vascular homeostasis.
authors: UNC McAllister Heart Institute, 8200 Medical Biomolecular Research Building, Chapel Hill, NC 27599-7126, USA.
authors: Xinchun
authors: X
authors: Pi
authors: Pamela
authors: P
authors: Lockyer
authors: Laura A
authors: LA
authors: Dyer
authors: Jonathan C
authors: JC
authors: Schisler
authors: Brooke
authors: B
authors: Russell
authors: Stephen
authors: S
authors: Carey
authors: Daniel Timothy
authors: DT
authors: Sweet
authors: Zhongming
authors: Z
authors: Chen
authors: Ellie
authors: E
authors: Tzima
authors: Monte S
authors: MS
authors: Willis
authors: Jonathon W
authors: JW
authors: Homeister
authors: Martin
authors: M
authors: Moser
authors: Cam
authors: C
authors: Patterson
mesh_terms: D000818:Animals; D001018:Aortic Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005838:Genotype; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D034622:RNA Interference; D011994:Recombinant Proteins / Q000378:metabolism; D013314:Stress, Mechanical; D013997:Time Factors; D014162:Transfection; D061205:Vascular Calcification / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; C525809:BMP4 protein, human; C476724:BMPER protein, human; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C573420:ICAM1 protein, human; D018836:Inflammation Mediators; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; C517553:crossveinless 2 protein, mouse; D018799:Intercellular Adhesion Molecule-1