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Blood, 1 September 2007, Vol. 110, No. 5, pp. 1502-1510. Prepublished online as a Blood First Edition Paper on May 11, 2007; DOI 10.1182/blood-2006-11-058594. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-11-058594v1 110/5/1502    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Liu, D. Articles by Li, E. Search for Related Content PubMed PubMed Citation Articles by Liu, D. Articles by Li, E. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 20, 2006 Accepted May 8, 2007 Dosage-dependent requirement of BMP type II receptor for maintenance of vascular integrity Dong Liu*, Jian Wang, Bernd Kinzel, Matthias Mueller, Xiaohong Mao, Reginald Valdez, Yongxing Liu, and En Li Developmental and Molecular Pathways, Novartis Institutes for Biomedical Research, Cambridge, MA, United States Developmental and Molecular Pathways, Novartis Institutes for Biomedical Research, Basel, Switzerland Models of Disease Center, Novartis Institutes for Biomedical Research, Cambridge, MA, United States * Corresponding author; email: dong.liu{at}novartis.com. Germline mutations in bone morphogenic protein type II receptor (Bmpr2) confer susceptibility to pulmonary arterial hypertension (PAH), which is characterized by obstructive vascular lesions in small arteries. The molecular and cellular mechanisms that account for the etiology of this disorder remain elusive, as is the role of Bmpr2 in postnatal tissue homeostasis. Here we show that in adult mice, stably silencing Bmpr2 expression by RNA interference does not increase pulmonary arterial resistance, but results in severe mucosal hemorrhage, incomplete mural cell coverage on vessel walls, and gastrointestinal hyperplasia. We present evidence that BMP receptor signaling regulates vascular remodeling during angiogenesis, by maintaining the expression of endothelial guidance molecules that promote vessel patterning and maturation, and by counteracting growth factor-induced AKT activation. Attenuation of this function may cause vascular dysmorphogenesis and predisposition to angioproliferative diseases. Our findings provide a mechanistic link between PAH and other diseases associated with BMP/TGF- pathways, such as hereditary hemorrhagic telangiectasia and juvenile polyposis syndrome. 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