Proceedings of the American Thoracic Society Email Content Delivery
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     


The Proceedings of the American Thoracic Society 3:680-686 (2006)
© 2006 The American Thoracic Society
doi: 10.1513/pats.200605-118SF

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Morrell, N. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Morrell, N. W.

Pulmonary Hypertension Due to BMPR2 Mutation

A New Paradigm for Tissue Remodeling?

Nicholas W. Morrell

Division of Respiratory Medicine, Department of Medicine, University of Cambridge, Cambridge, United Kingdom

Correspondence and requests for reprints should be addressed to Nicholas W. Morrell, M.A., M.D., F.R.C.P., Department of Medicine, University of Cambridge, Box 157, Level 5, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK. E-mail: nwm23{at}cam.ac.uk

ABSTRACT

Genetic studies in familial pulmonary arterial hypertension (FPAH) have revealed heterozygous germline mutations in the bone morphogenetic protein type II receptor (BMPR-II), a receptor for the transforming growth factor (TGF)-ß/bone morphogenetic protein (BMP) superfamily. PAH is characterized by intense remodeling of small pulmonary arteries by myofibroblast and smooth muscle proliferation. BMPR-II mutation in pulmonary artery smooth muscle cells contributes to abnormal growth responses to BMPs and TGF-ß. Reduced expression or function of BMPR-II signaling leads to exaggerated TGF-ß signaling and altered cellular responses to TGF-ß. The likely mechanism involves an interaction between BMP and TGF-ß–regulated Smad pathways. In endothelial cells, BMPR-II mutation increases the susceptibility of cells to apoptosis. The combination of increased endothelial apoptosis and failure of growth suppression in pulmonary artery smooth muscle cells provides important clues to the cellular pathogenesis of PAH. The reciprocal regulation of TGF-ß and BMP signaling in models of tissue repair may provide new approaches to our understanding of lung disease.

Key Words: genetics • pulmonary arterial hypertension • transforming growth factor-ß




This article has been cited by other articles:


Home page
Physiol. GenomicsHome page
L. Moreno-Vinasco, M. Gomberg-Maitland, M. L. Maitland, A. A. Desai, P. A. Singleton, S. Sammani, L. Sam, Y. Liu, A. N. Husain, R. M. Lang, et al.
Genomic assessment of a multikinase inhibitor, sorafenib, in a rodent model of pulmonary hypertension
Physiol Genomics, April 21, 2008; 33(2): 278 - 291.
[Abstract] [Full Text] [PDF]


Home page
ANN INTERN MEDHome page
J. H. Newman, J. A. Phillips III, and J. E. Loyd
Narrative Review: The Enigma of Pulmonary Arterial Hypertension: New Insights from Genetic Studies
Ann Intern Med, February 19, 2008; 148(4): 278 - 283.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
P. B. Yu, D. Y. Deng, H. Beppu, C. C. Hong, C. Lai, S. A. Hoyng, N. Kawai, and K. D. Bloch
Bone Morphogenetic Protein (BMP) Type II Receptor Is Required for BMP-mediated Growth Arrest and Differentiation in Pulmonary Artery Smooth Muscle Cells
J. Biol. Chem., February 15, 2008; 283(7): 3877 - 3888.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Respir. Cell Mol. Bio.Home page
P. B. Sehgal and S. Mukhopadhyay
Dysfunctional Intracellular Trafficking in the Pathobiology of Pulmonary Arterial Hypertension
Am. J. Respir. Cell Mol. Biol., July 1, 2007; 37(1): 31 - 37.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
P. B. Sehgal and S. Mukhopadhyay
Pulmonary arterial hypertension: a disease of tethers, SNAREs and SNAPs?
Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H77 - H85.
[Abstract] [Full Text] [PDF]


Home page
Ann. N. Y. Acad. Sci.Home page
D. E. FURST
Measuring Outcomes in PAH: The Gap between the Measures That Are Used and Their Validity
Ann. N.Y. Acad. Sci., June 1, 2007; 1107(1): 410 - 416.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2006 by the American Thoracic Society.