Bmper inhibits endothelial expression of inflammatory adhesion molecules and protects against atherosclerosis

Xinchun Pi, Pamela Lockyer, Laura A. Dyer, Jonathan C. Schisler, Brooke Russell, Stephen Carey, Daniel Timothy Sweet, Zhongming Chen, Ellie Tzima, Monte Willis, Jonathon W. Homeister, Martin Moser, Cam Patterson

Research output: Contribution to journalArticle

21 Citations (Scopus)

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. Methods and 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. Conclusion-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.

Original languageEnglish (US)
Pages (from-to)2214-2222
Number of pages9
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume32
Issue number9
DOIs
StatePublished - Sep 1 2012
Externally publishedYes

Fingerprint

Atherosclerosis
Apolipoproteins E
Inflammation
Blood Vessels
Endothelial Cells
Haploinsufficiency
Inflammation Mediators
Bone Morphogenetic Proteins
Vascular Cell Adhesion Molecule-1
Human Umbilical Vein Endothelial Cells
High Fat Diet
Thoracic Aorta
Small Interfering RNA
Homeostasis
Alleles
Maintenance
Parturition
Phenotype

Keywords

  • atherosclerosis
  • Bmp endothelial cell precursor-derived regulator
  • bone morphogenetic protein
  • fluid shear stress
  • inflammation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Bmper inhibits endothelial expression of inflammatory adhesion molecules and protects against atherosclerosis. / Pi, Xinchun; Lockyer, Pamela; Dyer, Laura A.; Schisler, Jonathan C.; Russell, Brooke; Carey, Stephen; Sweet, Daniel Timothy; Chen, Zhongming; Tzima, Ellie; Willis, Monte; Homeister, Jonathon W.; Moser, Martin; Patterson, Cam.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 32, No. 9, 01.09.2012, p. 2214-2222.

Research output: Contribution to journalArticle

Pi, X, Lockyer, P, Dyer, LA, Schisler, JC, Russell, B, Carey, S, Sweet, DT, Chen, Z, Tzima, E, Willis, M, Homeister, JW, Moser, M & Patterson, C 2012, 'Bmper inhibits endothelial expression of inflammatory adhesion molecules and protects against atherosclerosis', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 32, no. 9, pp. 2214-2222. https://doi.org/10.1161/ATVBAHA.112.252015
Pi, Xinchun ; Lockyer, Pamela ; Dyer, Laura A. ; Schisler, Jonathan C. ; Russell, Brooke ; Carey, Stephen ; Sweet, Daniel Timothy ; Chen, Zhongming ; Tzima, Ellie ; Willis, Monte ; Homeister, Jonathon W. ; Moser, Martin ; Patterson, Cam. / Bmper inhibits endothelial expression of inflammatory adhesion molecules and protects against atherosclerosis. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2012 ; Vol. 32, No. 9. pp. 2214-2222.
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AU - Lockyer, Pamela

AU - Dyer, Laura A.

AU - Schisler, Jonathan C.

AU - Russell, Brooke

AU - Carey, Stephen

AU - Sweet, Daniel Timothy

AU - Chen, Zhongming

AU - Tzima, Ellie

AU - Willis, Monte

AU - Homeister, Jonathon W.

AU - Moser, Martin

AU - Patterson, Cam

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AB - 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. Methods and 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. Conclusion-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.

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KW - fluid shear stress

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