Bmp2 and Bmp4 exert opposing effects in hypoxic pulmonary hypertension

American Journal of Physiology - Regulatory Integrative and Comparative Physiology

Volumn 298, Issue 3, 2010, Pages

  Anderson, Lynda ^a,b   Lowery, Jonathan W ^b   Frank, David B ^b   Novitskaya, Tatiana ^a   Jones, Mark ^a   Mortlock, Douglas P ^b   Chandler, Ronald L ^b   De Caestecker, Mark P ^a,b  

^a VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

^b VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Bone morphogenetic protein 2; Bone morphogenetic protein 4; Bone morphogenetic protein receptor 2; Endothelial nitric oxide synthase; Hypoxia; Pulmonary hypertension

Indexed keywords

BONE MORPHOGENETIC PROTEIN 2; BONE MORPHOGENETIC PROTEIN 4; ENDOTHELIAL NITRIC OXIDE SYNTHASE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DISEASE SEVERITY; ENZYME ACTIVATION; ENZYME ACTIVITY; HYPOXIA; LUNG BLOOD VESSEL; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; PULMONARY HYPERTENSION; WILD TYPE;

ANIMALS; ANOXIA; BONE MORPHOGENETIC PROTEIN 2; BONE MORPHOGENETIC PROTEIN 4; CELL DIVISION; HYPERTENSION, PULMONARY; LAC OPERON; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; NITRIC OXIDE SYNTHASE TYPE III; PULMONARY ARTERY; PULMONARY CIRCULATION; SIGNAL TRANSDUCTION;

EID: 77749328893     PISSN: 03636119     EISSN: 15221490     Source Type: Journal    
DOI: 10.1152/ajpregu.00534.2009     Document Type: Article

References (32)

1. Beppu H, Ichinose F, Kawai N, Jones RC, Yu PB, Zapol WM, Miyazono K, Li E, Bloch KD. BMPR-II heterozygous mice have mild pulmonary hypertension and an impaired pulmonary vascular remodeling response to prolonged hypoxia. Am J Physiol Lung Cell Mol Physiol 287: L1241-L1247, 2004.
2. Boyle S, Misfeldt A, Chandler KJ, Deal KK, Southard-Smith EM, Mortlock DP, Baldwin HS, de Caestecker M. Fate mapping using Cited1-CreERT2 mice demonstrates that the cap mesenchyme contains self-renewing progenitor cells and gives rise exclusively to nephronic epithelia. Dev Biol 313: 234-245, 2008.
3. Butt E, Abel K, Krieger M, Palm D, Hoppe V, Hoppe J, Walter U. cAMP- and cGMP-dependent protein kinase phosphorylation sites of the focal adhesion vasodilator-stimulated phosphoprotein (VASP) in vitro and in intact human platelets. J Biol Chem 269: 14509-14517, 1994.
4. Chandler RL, Chandler KJ, McFarland KA, Mortlock DP. Bmp2 transcription in osteoblast progenitors is regulated by a distant 3′ enhancer located 156.3 kilobases from the promoter. Mol Cell Biol 27: 2934-2951, 2007.
5. Coggins MP, Bloch KD. Nitric oxide in the pulmonary vasculature. Arterioscler Thromb Vasc Biol 27: 1877-1885, 2007.
6. de Caestecker M. The transforming growth factor-beta superfamily of receptors. Cytokine Growth Factor Rev 15: 1-11, 2004.
7. Dunn NR, Winnier GE, Hargett LK, Schrick JJ, Fogo AB, Hogan BL. Haploinsufficient phenotypes in Bmp4 heterozygous null mice and modification by mutations in Gli3 and Alx4. Dev Biol 188: 235-247, 1997.
8. El-Bizri N, Wang L, Merklinger SL, Guignabert C, Desai T, Urashima T, Sheikh AY, Knutsen RH, Mecham RP, Mishina Y, Rabinovitch M. Smooth muscle protein 22alpha-mediated patchy deletion of Bmpr1a impairs cardiac contractility but protects against pulmonary vascular remodeling. Circ Res 102: 380-388, 2008.
9. Fagan KA, Fouty BW, Tyler RC, Morris KG Jr, Hepler LK, Sato K, LeCras TD, Abman SH, Weinberger HD, Huang PL, McMurtry IF, Rodman DM. The pulmonary circulation of homozygous or heterozygous eNOS-null mice is hyperresponsive to mild hypoxia. J Clin Invest 103: 291-299, 1999.
10. Frank DB, Abtahi A, Yamaguchi DJ, Manning S, Shyr Y, Pozzi A, Baldwin HS, Johnson JE, de Caestecker MP. Bone morphogenetic protein 4 promotes pulmonary vascular remodeling in hypoxic pulmonary hypertension. Circ Res 97: 496-504, 2005.
11. Frank DB, Lowery J, Anderson L, Brink M, Reese J, de Caestecker M. Increased susceptibility to hypoxic pulmonary hypertension in Bmpr2 mutant mice is associated with endothelial dysfunction in the pulmonary vasculature. Am J Physiol Lung Cell Mol Physiol 294: L98-L109, 2008.
12. Hagen M, Fagan K, Steudel W, Carr M, Lane K, Rodman DM, West J. Interaction of interleukin-6 and the BMP pathway in pulmonary smooth muscle. Am J Physiol Lung Cell Mol Physiol 292: L1473-L1479, 2007.
13. Hong KH, Lee YJ, Lee E, Park SO, Han C, Beppu H, Li E, Raizada MK, Bloch KD, Oh SP. Genetic ablation of the BMPR2 gene in pulmonary endothelium is sufficient to predispose to pulmonary arterial hypertension. Circulation 118: 722-730, 2008.
14. Jat PS, Noble MD, Ataliotis P, Tanaka Y, Yannoutsos N, Larsen L, Kioussis D. Direct derivation of conditionally immortal cell lines from an H-2Kb-tsA58 transgenic mouse. Proc Natl Acad Sci USA 88: 5096-5100, 1991.
15. Lawson KA, Dunn NR, Roelen BA, Zeinstra LM, Davis AM, Wright CV, Korving JP, Hogan BL. Bmp4 is required for the generation of primordial germ cells in the mouse embryo. Genes Dev 13: 424-436, 1999.
16. Long L, MacLean MR, Jeffery TK, Morecroft I, Yang X, Rudarakanchana N, Southwood M, James V, Trembath RC, Morrell NW. Serotonin increases susceptibility to pulmonary hypertension in BMPR2-deficient mice. Circ Res 98: 818-827, 2006.
17. Machado RD, Pauciulo MW, Thomson JR, Lane KB, Morgan NV, Wheeler L, Phillips JA, 3rd Newman J, Williams D, Galie N, Manes A, McNeil K, Yacoub M, Mikhail G, Rogers P, Corris P, Humbert M, Donnai D, Martensson G, Tranebjaerg L, Loyd JE, Trembath RC, Nichols WC. BMPR2 haploinsufficiency as the inherited molecular mechanism for primary pulmonary hypertension. Am J Hum Genet 68: 92-102, 2001.
18. Meyrick BO, Perkett EA. The sequence of cellular and hemodynamic changes of chronic pulmonary hypertension induced by hypoxia and other stimuli. Am Rev Respir Dis 140: 1486-1489, 1989.
19. Morrell NW, Yang X, Upton PD, Jourdan KB, Morgan N, Sheares KK, Trembath RC. Altered growth responses of pulmonary artery smooth muscle cells from patients with primary pulmonary hypertension to transforming growth factor-beta(1) and bone morphogenetic proteins. Circulation 104: 790-795, 2001.
20. Oelze M, Mollnau H, Hoffmann N, Warnholtz A, Bodenschatz M, Smolenski A, Walter U, Skatchkov M, Meinertz T, Munzel T. Vasodilator-stimulated phosphoprotein serine 239 phosphorylation as a sensitive monitor of defective nitric oxide/cGMP signaling and endothelial dysfunction. Circ Res 87: 999-1005, 2000.
21. Quinlan TR, Li D, Laubach VE, Shesely EG, Zhou N, Johns RA. eNOS-deficient mice show reduced pulmonary vascular proliferation and remodeling to chronic hypoxia. Am J Physiol Lung Cell Mol Physiol 279: L641-L650, 2000.
22. Song Y, Coleman L, Shi J, Beppu H, Sato K, Walsh K, Loscalzo J, Zhang YY. Inflammation, endothelial injury, and persistent pulmonary hypertension in heterozygous BMPR2-mutant mice. Am J Physiol Heart Circ Physiol 295: H677-H690, 2008.
23. Song Y, Jones JE, Beppu H, Keaney JF Jr, Loscalzo J, Zhang YY. Increased susceptibility to pulmonary hypertension in heterozygous BMPR2-mutant mice. Circulation 112: 553-562, 2005.
24. Steudel W, Ichinose F, Huang PL, Hurford WE, Jones RC, Bevan JA, Fishman MC, Zapol WM. Pulmonary vasoconstriction and hypertension in mice with targeted disruption of the endothelial nitric oxide synthase (NOS 3) gene. Circ Res 81: 34-41, 1997.
25. Steudel W, Scherrer-Crosbie M, Bloch KD, Weimann J, Huang PL, Jones RC, Picard MH, Zapol WM. Sustained pulmonary hypertension and right ventricular hypertrophy after chronic hypoxia in mice with congenital deficiency of nitric oxide synthase 3. J Clin Invest 101: 2468-2477, 1998.
26. Takeda M, Otsuka F, Nakamura K, Inagaki K, Suzuki J, Miura D, Fujio H, Matsubara H, Date H, Ohe T, Makino H. Characterization of the bone morphogenetic protein (BMP) system in human pulmonary arterial smooth muscle cells isolated from a sporadic case of primary pulmonary hypertension: roles of BMP type IB receptor (activin receptor-like kinase-6) in the mitotic action. Endocrinology 145: 4344-4354, 2004.
27. Upton PD, Morrell NW. TGF-beta and BMPR-II pharmacology- implications for pulmonary vascular diseases. Curr Opin Pharmacol 9: 274-280, 2009.
28. West J, Fagan K, Steudel W, Fouty B, Lane K, Harral J, Hoedt-Miller M, Tada Y, Ozimek J, Tuder R, Rodman DM. Pulmonary hypertension in transgenic mice expressing a dominant-negative BMPRII gene in smooth muscle. Circ Res 94: 1109-1114, 2004.
29. Winnier G, Blessing M, Labosky PA, Hogan BL. Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev 9: 2105-2116, 1995.
30. Yang X, Long L, Southwood M, Rudarakanchana N, Upton PD, Jeffery TK, Atkinson C, Chen H, Trembath RC, Morrell NW. Dysfunctional Smad signaling contributes to abnormal smooth muscle cell proliferation in familial pulmonary arterial hypertension. Circ Res 96: 1053-1063, 2005.
31. Zhang H, Bradley A. Mice deficient for BMP2 are nonviable and have defects in amnion/chorion and cardiac development. Development 122: 2977-2986, 1996.
32. Zhang S, Fantozzi I, Tigno DD, Yi ES, Platoshyn O, Thistlethwaite PA, Kriett JM, Yung G, Rubin LJ, Yuan JX. Bone morphogenetic proteins induce apoptosis in human pulmonary vascular smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 285: L740-L754, 2003.