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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. 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.

Original publication

DOI

10.1161/ATVBAHA.112.252015

Type

Journal article

Journal

Arterioscler Thromb Vasc Biol

Publication Date

09/2012

Volume

32

Pages

2214 - 2222

Keywords

Animals, Aortic Diseases, Apolipoproteins E, Atherosclerosis, Bone Morphogenetic Protein 4, Carrier Proteins, Cell Adhesion Molecules, Cells, Cultured, Disease Models, Animal, Endothelial Cells, Genotype, Human Umbilical Vein Endothelial Cells, Humans, Inflammation, Inflammation Mediators, Intercellular Adhesion Molecule-1, Mice, Mice, Inbred C57BL, Mice, Knockout, Phenotype, RNA Interference, Recombinant Proteins, Stress, Mechanical, Time Factors, Transfection, Vascular Calcification, Vascular Cell Adhesion Molecule-1