title: BMPER regulates cardiomyocyte size and vessel density in vivo.
abstract: BACKGROUND
  BMPER, an orthologue of Drosophila melanogaster Crossveinless-2, is a secreted factor that regulates bone morphogenetic protein activity in endothelial cell precursors and during early cardiomyocyte differentiation. Although previously described in the heart, the role of BMPER in cardiac development and function remain unknown.
  
  
  METHODS
  BMPER-deficient hearts were phenotyped histologically and functionally using echocardiography and Doppler analysis. Since BMPER -/- mice die perinatally, adult BMPER +/- mice were challenged to pressure-overload-induced cardiac hypertrophy and hindlimb ischemia to determine changes in angiogenesis and regulation of cardiomyocyte size.
  
  
  RESULTS
  We identify for the first time the cardiac phenotype associated with BMPER haploinsufficiency. BMPER messenger RNA and protein are present in the heart during cardiac development through at least E14.5 but is lost by E18.5. BMPER +/- ventricles are thinner and less compact than sibling wild-type hearts. In the adult, BMPER +/- hearts present with decreased anterior and posterior wall thickness, decreased cardiomyocyte size and an increase in cardiac vessel density. Despite these changes, BMPER +/- mice respond to pressure-overload-induced cardiac hypertrophy challenge largely to the same extent as wild-type mice.
  
  
  CONCLUSIONS
  BMPER appears to play a role in regulating both vessel density and cardiac development in vivo; however, BMPER haploinsufficiency does not result in marked effects on cardiac function or adaptation to pressure overload hypertrophy.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Monte S
authors.initials: MS
authors.lastname: Willis
authors.forename: Laura A
authors.initials: LA
authors.lastname: Dyer
authors.forename: Rongqin
authors.initials: R
authors.lastname: Ren
authors.forename: Pamela
authors.initials: P
authors.lastname: Lockyer
authors.forename: Isabel
authors.initials: I
authors.lastname: Moreno-Miralles
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Schisler
authors.forename: Cam
authors.initials: C
authors.lastname: Patterson
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006332:Cardiomegaly / Q000473:pathology / Q000503:physiopathology; D002352:Carrier Proteins / Q000378:metabolism*; D049108:Cell Enlargement; D003331:Coronary Vessels / Q000378:metabolism; D006321:Heart / Q000254:growth & development*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D002352:Carrier Proteins; C517553:crossveinless 2 protein, mouse