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.
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. Bmperhaploinsufficiency 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: Matthias Derwall; Rajeev Malhotra; Carol S Lai; Yuko Beppu; Elena Aikawa; Jasbir S Seehra; Warren M Zapol; Kenneth D Bloch; Paul B Yu Journal: Arterioscler Thromb Vasc Biol Date: 2012-01-05 Impact factor: 8.311
Authors: Kyunghwa Chang; Daiana Weiss; Jin Suo; J David Vega; Don Giddens; W Robert Taylor; Hanjoong Jo Journal: Circulation Date: 2007-09-04 Impact factor: 29.690
Authors: Thomas Helbing; Gwendoline Wiltgen; Alexandra Hornstein; Elena Z Brauers; Linus Arnold; Adrian Bauer; Jennifer S Esser; Philipp Diehl; Sebastian Grundmann; Katrin Fink; Cam Patterson; Christoph Bode; Martin Moser Journal: Inflammation Date: 2017-04 Impact factor: 4.092
Authors: Monte S Willis; Laura A Dyer; Rongqin Ren; Pamela Lockyer; Isabel Moreno-Miralles; Jonathan C Schisler; Cam Patterson Journal: Cardiovasc Pathol Date: 2012-11-28 Impact factor: 2.185
Authors: Khaled A Hussein; Karishma Choksi; Sara Akeel; Saif Ahmad; Sylvia Megyerdi; Mohamed El-Sherbiny; Mohamed Nawaz; Ahmed Abu El-Asrar; Mohamed Al-Shabrawey Journal: Exp Eye Res Date: 2014-06-06 Impact factor: 3.467
Authors: Lehanna N Sanders; John A Schoenhard; Mohamed A Saleh; Amrita Mukherjee; Sergey Ryzhov; William G McMaster; Kristof Nolan; Richard J Gumina; Thomas B Thompson; Mark A Magnuson; David G Harrison; Antonis K Hatzopoulos Journal: Circ Res Date: 2016-06-09 Impact factor: 17.367
Authors: Ine Vandersmissen; Sander Craps; Maarten Depypere; Giulia Coppiello; Nick van Gastel; Frederik Maes; Geert Carmeliet; Jan Schrooten; Elizabeth A V Jones; Lieve Umans; Roland Devlieger; Michel Koole; Olivier Gheysens; An Zwijsen; Xabier L Aranguren; Aernout Luttun Journal: J Cell Biol Date: 2015-09-21 Impact factor: 10.539