title: Bone morphogenetic protein endothelial cell precursor-derived regulator regulates retinal angiogenesis in vivo in a mouse model of oxygen-induced retinopathy.
abstract: OBJECTIVE
  Bone morphogenetic proteins (BMPs) are potently proangiogenic; however, the mechanisms underlying the regulation of vessel development by BMPs are not fully understood. To assess the significance of BMP endothelial cell precursor-derived regulator (BMPER) in blood vessel formation in vivo, we investigated its role in retinal angiogenesis.
  
  
  RESULTS
  In a model of oxygen-induced retinopathy, Bmper mRNA expression and protein levels are downregulated, correlating with the initiation of Sma and Mad related protein phosphorylation in endothelial cells. Moreover, Bmper haploinsufficiency results in an increased rate of retinal revascularization, with retinas from Bmper+/- mice displaying increased numbers of branching points and angiogenic sprouts at the leading edge of the newly formed vasculature. Furthermore, although Bmper haploinsufficiency does not alter Bmp expression, it does lead to an increase in BMP signaling, as evidenced by increased phosphorylated Sma and Mad related protein levels in endothelial cells and increased expression of known BMP target genes.
  
  
  CONCLUSIONS
  These observations provide compelling evidence that BMPER is important in the regulation of BMP signaling and revascularization in the hypoxic retina. These bring forth the possibility of novel therapeutic approaches for pathological angiogenesis based on manipulation of BMP signaling.
authors: McAllister Heart Institute, University of North Carolina at Chapel Hill, USA.
authors: Isabel
authors: I
authors: Moreno-Miralles
authors: Rongqin
authors: R
authors: Ren
authors: Martin
authors: M
authors: Moser
authors: Mary Elizabeth
authors: ME
authors: Hartnett
authors: Cam
authors: C
authors: Patterson
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000235:genetics; D010100:Oxygen; D020286:Pericytes / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D015861:Retinal Neovascularization / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D012171:Retinal Vessels / Q000378:metabolism* / Q000503:physiopathology; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D012333:RNA, Messenger; D051785:Smad Proteins; C517553:crossveinless 2 protein, mouse; D010100:Oxygen