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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 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 Citation Map 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. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Dosage-dependent requirement of BMP type II receptor for maintenance of vascular integrity Dong Liu1, Jian Wang1, Bernd Kinzel2, Matthias Müeller2, Xiaohong Mao1, Reginald Valdez1, Yongxing Liu1, and En Li3 1 Developmental and Molecular Pathways, Novartis Institutes for Biomedical Research, Cambridge, MA; 2 Developmental and Molecular Pathways, Novartis Institutes for Biomedical Research, Basel, Switzerland; and 3 Models of Disease Center, Novartis Institutes for Biomedical Research, Cambridge, MA Germ-line 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 does 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 the BMP/TGF-β pathways, such as hereditary hemorrhagic telangiectasia and juvenile polyposis syndrome. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. R. Stenmark, B. Meyrick, N. Galie, W. J. Mooi, and I. F. McMurtry Animal models of pulmonary arterial hypertension: the hope for etiological discovery and pharmacological cure Am J Physiol Lung Cell Mol Physiol, December 1, 2009; 297(6): L1013 - L1032. [Abstract] [Full Text] [PDF] N. W. Morrell, S. Adnot, S. L. Archer, J. Dupuis, P. Lloyd Jones, M. R. MacLean, I. F. McMurtry, K. R. Stenmark, P. A. Thistlethwaite, N. Weissmann, et al. Cellular and molecular basis of pulmonary arterial hypertension. J. Am. Coll. Cardiol., June 30, 2009; 54(1 Suppl): S20 - S31. [Abstract] [Full Text] [PDF] J. West, J. Harral, K. Lane, Y. Deng, B. Ickes, D. Crona, S. Albu, D. Stewart, and K. Fagan Mice expressing BMPR2R899X transgene in smooth muscle develop pulmonary vascular lesions Am J Physiol Lung Cell Mol Physiol, November 1, 2008; 295(5): L744 - L755. 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