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Bmp2 and Bmp4 exert opposing effects in hypoxic pulmonary hypertension

Bmp2 and Bmp4 exert opposing effects in hypoxic pulmonary hypertension Abstract The bone morphogenetic protein (BMP) type 2 receptor ligand, Bmp2, is upregulated in the peripheral pulmonary vasculature during hypoxia-induced pulmonary hypertension (PH). This contrasts with the expression of Bmp4, which is expressed in respiratory epithelia throughout the lung. Unlike heterozygous null Bmp4 mice ( Bmp4 LacZ/+ ), which are protected from the development of hypoxic PH, mice that are heterozygous null for Bmp2 ( Bmp2 +/− ) develop more severe hypoxic PH than their wild-type littermates. This is associated with reduced endothelial nitric oxide synthase (eNOS) expression and activity in the pulmonary vasculature of hypoxic Bmp2 +/− but not Bmp4 LacZ/+ mutant mice. Furthermore, exogenous BMP2 upregulates eNOS expression and activity in intrapulmonary artery and pulmonary endothelial cell preparations, indicating that eNOS is a target of Bmp2 signaling in the pulmonary vasculature. Together, these data demonstrate that Bmp2 and Bmp4 exert opposing roles in hypoxic PH and suggest that the protective effects of Bmp2 are mediated by increasing eNOS expression and activity in the hypoxic pulmonary vasculature. hypoxia pulmonary hypertension bone morphogenetic protein 2 bone morphogenetic protein 4 bone morphogenetic protein receptor 2 endothelial nitric oxide synthase Footnotes http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Regulatory, Integrative and Comparative Physiology The American Physiological Society

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References (33)

Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0363-6119
eISSN
1522-1490
DOI
10.1152/ajpregu.00534.2009
pmid
20042692
Publisher site
See Article on Publisher Site

Abstract

Abstract The bone morphogenetic protein (BMP) type 2 receptor ligand, Bmp2, is upregulated in the peripheral pulmonary vasculature during hypoxia-induced pulmonary hypertension (PH). This contrasts with the expression of Bmp4, which is expressed in respiratory epithelia throughout the lung. Unlike heterozygous null Bmp4 mice ( Bmp4 LacZ/+ ), which are protected from the development of hypoxic PH, mice that are heterozygous null for Bmp2 ( Bmp2 +/− ) develop more severe hypoxic PH than their wild-type littermates. This is associated with reduced endothelial nitric oxide synthase (eNOS) expression and activity in the pulmonary vasculature of hypoxic Bmp2 +/− but not Bmp4 LacZ/+ mutant mice. Furthermore, exogenous BMP2 upregulates eNOS expression and activity in intrapulmonary artery and pulmonary endothelial cell preparations, indicating that eNOS is a target of Bmp2 signaling in the pulmonary vasculature. Together, these data demonstrate that Bmp2 and Bmp4 exert opposing roles in hypoxic PH and suggest that the protective effects of Bmp2 are mediated by increasing eNOS expression and activity in the hypoxic pulmonary vasculature. hypoxia pulmonary hypertension bone morphogenetic protein 2 bone morphogenetic protein 4 bone morphogenetic protein receptor 2 endothelial nitric oxide synthase Footnotes

Journal

AJP - Regulatory, Integrative and Comparative PhysiologyThe American Physiological Society

Published: Mar 1, 2010

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