NDLI: Crossveinless 2 regulates bone morphogenetic protein 9 in human and mouse vascular endothelium

Content Provider	PubMed Central
Author	Yao, Yucheng Jumabay, Medet Ly, Albert Melina, Radparvar Wang, Anthony H. Abdmaulen, Raushan Boström, Kristina I.
Copyright Year	2012
Abstract	The importance of morphogenetic proteins (BMPs) and their antagonists in vascular development is increasingly being recognized. BMP-4 is essential for angiogenesis and is antagonized by matrix Gla protein (MGP) and crossveinless 2 (CV2), both induced by the activin receptor like-kinase 1 (ALK1) when stimulated by BMP-9. In this study, however, we show that CV2 preferentially binds and inhibits BMP-9 thereby providing strong feedback inhibition for BMP-9/ALK1 signaling rather than for BMP-4/ALK2 signaling. CV2 disrupts complex formation involving ALK2, ALK1, BMP-4, and BMP-9 required for the induction of both BMP antagonists. It also limits VEGF expression, proliferation, and tube formation in ALK1-expressing endothelial cells. In vivo, CV2 deficiency translates into a dysregulation of vascular BMP signaling, resulting in an abnormal endothelium with increased endothelial cellularity and expression of lineage markers for mature endothelial cells. Thus, mutual regulation by BMP-9 and CV2 is essential in regulating the development of the vascular endothelium.
Related Links	http://dx.doi.org/10.1182/blood-2011-10-385906
Ending Page	5047
Page Count	11
Starting Page	5037
File Format	PDF
ISSN	00064971
e-ISSN	15280020
Journal	Blood
Issue Number	21
Volume Number	119
Language	English
Publisher	American Society of Hematology
Publisher Date	2012-05-24
Access Restriction	Open
Rights Holder	American Society of Hematology
Subject Keyword	Immunology Cell Biology Biochemistry Hematology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Hematology Biochemistry Immunology

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