BMPER regulates cardiomyocyte size and vessel density in vivo

Monte S. Willis, Laura A. Dyer, Rongqin Ren, Pamela Lockyer, Isabel Moreno-Miralles, Jonathan C. Schisler, Cam Patterson

Research output: Contribution to journalArticle

6 Scopus citations

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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)228-240
Number of pages13
JournalCardiovascular Pathology
Volume22
Issue number3
DOIs
StatePublished - May 1 2013

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Keywords

  • Angiogenesis
  • BMP
  • BMPER
  • Cell size
  • Development
  • Heart

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Willis, M. S., Dyer, L. A., Ren, R., Lockyer, P., Moreno-Miralles, I., Schisler, J. C., & Patterson, C. (2013). BMPER regulates cardiomyocyte size and vessel density in vivo. Cardiovascular Pathology, 22(3), 228-240. https://doi.org/10.1016/j.carpath.2012.10.005