| First Author | Yao Y | Year | 2012 |
| Journal | Blood | Volume | 119 |
| Issue | 21 | Pages | 5037-47 |
| PubMed ID | 22474252 | Mgi Jnum | J:185158 |
| Mgi Id | MGI:5427543 | Doi | 10.1182/blood-2011-10-385906 |
| Citation | Yao Y, et al. (2012) Crossveinless 2 regulates bone morphogenetic protein 9 in human and mouse vascular endothelium. Blood 119(21):5037-47 |
| abstractText | 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. |
