Circulation. 2001;104:790-795
doi: 10.1161/hc3201.094152
doi: 10.1161/hc3201.094152
(Circulation. 2001;104:790.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Altered Growth Responses of Pulmonary Artery Smooth Muscle Cells From Patients With Primary Pulmonary Hypertension to Transforming Growth Factor-ß1 and Bone Morphogenetic Proteins
From the Department of Medicine (N.W.M., X.Y., P.D.U., K.B.J., N.M., K.K.S.), University of Cambridge, Addenbrooke’s and Papworth Hospitals, Cambridge, United Kingdom; and Division of Clinical Genetics (R.C.T.), University of Leicester, Leicester, United Kingdom.
Correspondence to Dr Nicholas W. Morrell, Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke’s Hospital, Box 157, Hills Rd, Cambridge CB2 2QQ, UK. E-mail nwm23{at}cam.ac.uk
Background— Mutations in the type II receptor for bone morphogenetic protein (BMPR-II), a receptor member of the transforming growth factor-ß (TGF-ß) superfamily, underlie many cases of familial and sporadic primary pulmonary hypertension (PPH). We postulated that pulmonary artery smooth muscle cells (PASMCs) from patients with PPH might demonstrate abnormal growth responses to TGF-ß superfamily members.
Methods and Results— For studies of 3H-thymidine incorporation or cell proliferation, PASMCs (passages 4 to 8) were derived from main pulmonary arteries. In control cells, 24-hour incubation with TGF-ß1 (10 ng/mL) or bone morphogenetic protein (BMP)-2, -4, and -7 (100 ng/mL) inhibited basal and serum-stimulated 3H-thymidine incorporation, and TGF-ß1 and BMPs inhibited the proliferation of serum-stimulated PASMCs. In contrast, TGF-ß1 stimulated 3H-thymidine incorporation (200%; P<0.001) and cell proliferation in PASMCs from PPH but not from patients with secondary pulmonary hypertension. In addition, BMPs failed to suppress DNA synthesis and proliferation in PASMCs from PPH patients. Reverse transcription–polymerase chain reaction of PASMC mRNA detected transcripts for type I (TGF-ßRI, Alk-1, ActRI, and BMPRIB) and type II (TGF-ßRII, BMPR-II, ActRII, ActRIIB) receptors. Receptor binding and cross-linking studies with 125I-TGF-ß1 confirmed that the abnormal responses in PPH cells were not due to differences in TGF-ß receptor binding. Mutation analysis of PASMC DNA failed to detect mutations in TGF-ßRII and Alk-1 but confirmed the presence of a mutation in BMPR-II in 1 of 5 PPH isolates.
Conclusions— We conclude that PASMCs from patients with PPH exhibit abnormal growth responses to TGF-ß1 and BMPs and that altered integration of TGF-ß superfamily growth signals may contribute to the pathogenesis of PPH.
Key Words: hypertension, pulmonary • muscle, smooth • growth substances • proteins
This article has been cited by other articles:
 |
|
 |
|
  E. D. Michelakis, M. R. Wilkins, and M. Rabinovitch Emerging Concepts and Translational Priorities in Pulmonary Arterial Hypertension Circulation, September 30, 2008; 118(14): 1486 - 1495. [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Zaiman, M. Podowski, S. Medicherla, K. Gordy, F. Xu, L. Zhen, L. A. Shimoda, E. Neptune, L. Higgins, A. Murphy, et al. Role of the TGF-{beta}/Alk5 Signaling Pathway in Monocrotaline-induced Pulmonary Hypertension Am. J. Respir. Crit. Care Med., April 15, 2008; 177(8): 896 - 905. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. El-Haroun, D. L. Clarke, K. Deacon, D. Bradbury, A. Clayton, A. Sutcliffe, and A. J. Knox IL-1{beta}, BK, and TGF-{beta}1 attenuate PGI2-mediated cAMP formation in human pulmonary artery smooth muscle cells by multiple mechanisms involving p38 MAP kinase and PKA Am J Physiol Lung Cell Mol Physiol, March 1, 2008; 294(3): L553 - L562. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Asosingh, M. A. Aldred, A. Vasanji, J. Drazba, J. Sharp, C. Farver, S. A.A. Comhair, W. Xu, L. Licina, L. Huang, et al. Circulating Angiogenic Precursors in Idiopathic Pulmonary Arterial Hypertension Am. J. Pathol., March 1, 2008; 172(3): 615 - 627. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 P. D. Upton, L. Long, R. C. Trembath, and N. W. Morrell Functional Characterization of Bone Morphogenetic Protein Binding Sites and Smad1/5 Activation in Human Vascular Cells Mol. Pharmacol., February 1, 2008; 73(2): 539 - 552. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Suzuki, K. Montagne, A. Nishihara, T. Watabe, and K. Miyazono BMPs Promote Proliferation and Migration of Endothelial Cells via Stimulation of VEGF-A/VEGFR2 and Angiopoietin-1/Tie2 Signalling J. Biochem., February 1, 2008; 143(2): 199 - 206. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Archer, M. Gomberg-Maitland, M. L. Maitland, S. Rich, J. G. N. Garcia, and E. K. Weir Mitochondrial metabolism, redox signaling, and fusion: a mitochondria-ROS-HIF-1{alpha}-Kv1.5 O2-sensing pathway at the intersection of pulmonary hypertension and cancer Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H570 - H578. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. B. Frank, J. Lowery, L. Anderson, M. Brink, J. Reese, and M. de Caestecker 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, January 1, 2008; 294(1): L98 - L109. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Lawrie, E. Waterman, M. Southwood, D. Evans, J. Suntharalingam, S. Francis, D. Crossman, P. Croucher, N. Morrell, and C. Newman Evidence of a Role for Osteoprotegerin in the Pathogenesis of Pulmonary Arterial Hypertension Am. J. Pathol., January 1, 2008; 172(1): 256 - 264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Lagna, M. M. Ku, P. H. Nguyen, N. A. Neuman, B. N. Davis, and A. Hata Control of Phenotypic Plasticity of Smooth Muscle Cells by Bone Morphogenetic Protein Signaling through the Myocardin-related Transcription Factors J. Biol. Chem., December 21, 2007; 282(51): 37244 - 37255. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Zhou, J. Heinke, A. Vargas, S. Winnik, T. Krauss, C. Bode, C. Patterson, and M. Moser ERK signaling is a central regulator for BMP-4 dependent capillary sprouting Cardiovasc Res, December 1, 2007; 76(3): 390 - 399. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Sanchez, E. Marcos, F. Perros, E. Fadel, L. Tu, M. Humbert, P. Dartevelle, G. Simonneau, S. Adnot, and S. Eddahibi Role of Endothelium-derived CC Chemokine Ligand 2 in Idiopathic Pulmonary Arterial Hypertension Am. J. Respir. Crit. Care Med., November 15, 2007; 176(10): 1041 - 1047. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Yang, P. J. Lee, L. Long, R. C. Trembath, and N. W. Morrell BMP4 Induces HO-1 via a Smad-Independent, p38MAPK-Dependent Pathway in Pulmonary Artery Myocytes Am. J. Respir. Cell Mol. Biol., November 1, 2007; 37(5): 598 - 605. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Ito, T. Okada, H. Miyashita, T. Nomoto, M. Nonaka-Sarukawa, R. Uchibori, Y. Maeda, M. Urabe, H. Mizukami, A. Kume, et al. Interleukin-10 Expression Mediated by an Adeno-Associated Virus Vector Prevents Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats Circ. Res., September 28, 2007; 101(7): 734 - 741. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Liu, J. Wang, B. Kinzel, M. Mueller, X. Mao, R. Valdez, Y. Liu, and E. Li Dosage-dependent requirement of BMP type II receptor for maintenance of vascular integrity Blood, September 1, 2007; 110(5): 1502 - 1510. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Zhao, Z. Liu, Z. Wang, C. Yang, J. Liu, and J. Lu Effect of Prepro-Calcitonin Gene-Related Peptide Expressing Endothelial Progenitor Cells on Pulmonary Hypertension Ann. Thorac. Surg., August 1, 2007; 84(2): 544 - 552. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zakrzewicz, M. Hecker, L. M. Marsh, G. Kwapiszewska, B. Nejman, L. Long, W. Seeger, R. T. Schermuly, N. W. Morrell, R. E. Morty, et al. Receptor for Activated C-Kinase 1, a Novel Interaction Partner of Type II Bone Morphogenetic Protein Receptor, Regulates Smooth Muscle Cell Proliferation in Pulmonary Arterial Hypertension Circulation, June 12, 2007; 115(23): 2957 - 2968. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zakrzewicz, F. M. Kouri, B. Nejman, G. Kwapiszewska, M. Hecker, R. Sandu, E. Dony, W. Seeger, R. T. Schermuly, O. Eickelberg, et al. The transforming growth factor-{beta}/Smad2,3 signalling axis is impaired in experimental pulmonary hypertension Eur. Respir. J., June 1, 2007; 29(6): 1094 - 1104. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Zhang, H. Dong, L. J. Rubin, and J. X.-J. Yuan Upregulation of Na+/Ca2+ exchanger contributes to the enhanced Ca2+ entry in pulmonary artery smooth muscle cells from patients with idiopathic pulmonary arterial hypertension Am J Physiol Cell Physiol, June 1, 2007; 292(6): C2297 - C2305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. E. Morty, B. Nejman, G. Kwapiszewska, M. Hecker, A. Zakrzewicz, F. M. Kouri, D. M. Peters, R. Dumitrascu, W. Seeger, P. Knaus, et al. Dysregulated Bone Morphogenetic Protein Signaling in Monocrotaline-Induced Pulmonary Arterial Hypertension Arterioscler. Thromb. Vasc. Biol., May 1, 2007; 27(5): 1072 - 1078. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Reynolds, W. Xia, M. D. Holmes, S. J. Hodge, S. Danilov, D. T. Curiel, N. W. Morrell, and P. N. Reynolds Bone morphogenetic protein type 2 receptor gene therapy attenuates hypoxic pulmonary hypertension Am J Physiol Lung Cell Mol Physiol, May 1, 2007; 292(5): L1182 - L1192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. McMurtry, R. Moudgil, K. Hashimoto, S. Bonnet, E. D. Michelakis, and S. L. Archer Overexpression of human bone morphogenetic protein receptor 2 does not ameliorate monocrotaline pulmonary arterial hypertension Am J Physiol Lung Cell Mol Physiol, April 1, 2007; 292(4): L872 - L878. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. W. Morrell Pulmonary Hypertension Due to BMPR2 Mutation: A New Paradigm for Tissue Remodeling? Proceedings of the ATS, November 1, 2006; 3(8): 680 - 686. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Lagna, P. H. Nguyen, W. Ni, and A. Hata BMP-dependent activation of caspase-9 and caspase-8 mediates apoptosis in pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L1059 - L1067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Fantozzi, O. Platoshyn, A. H. Wong, S. Zhang, C. V. Remillard, M. R. Furtado, O. V. Petrauskene, and J. X.-J. Yuan Bone morphogenetic protein-2 upregulates expression and function of voltage-gated K+ channels in human pulmonary artery smooth muscle cells Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L993 - L1004. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ihida-Stansbury, D. M. McKean, K. B. Lane, J. E. Loyd, L. A. Wheeler, N. W. Morrell, and P. L. Jones Tenascin-C is induced by mutated BMP type II receptors in familial forms of pulmonary arterial hypertension Am J Physiol Lung Cell Mol Physiol, October 1, 2006; 291(4): L694 - L702. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bobik Transforming Growth Factor-{beta}s and Vascular Disorders Arterioscler. Thromb. Vasc. Biol., August 1, 2006; 26(8): 1712 - 1720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Miriyala, M. C. Gongora Nieto, C. Mingone, D. Smith, S. Dikalov, D. G. Harrison, and H. Jo Bone Morphogenic Protein-4 Induces Hypertension in Mice: Role of Noggin, Vascular NADPH Oxidases, and Impaired Vasorelaxation Circulation, June 20, 2006; 113(24): 2818 - 2825. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bonnet, E. D. Michelakis, C. J. Porter, M. A. Andrade-Navarro, B. Thebaud, S. Bonnet, A. Haromy, G. Harry, R. Moudgil, M. S. McMurtry, et al. An Abnormal Mitochondrial-Hypoxia Inducible Factor-1{alpha}-Kv Channel Pathway Disrupts Oxygen Sensing and Triggers Pulmonary Arterial Hypertension in Fawn Hooded Rats: Similarities to Human Pulmonary Arterial Hypertension Circulation, June 6, 2006; 113(22): 2630 - 2641. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Eddahibi, C. Guignabert, A.-M. Barlier-Mur, L. Dewachter, E. Fadel, P. Dartevelle, M. Humbert, G. Simonneau, N. Hanoun, F. Saurini, et al. Cross Talk Between Endothelial and Smooth Muscle Cells in Pulmonary Hypertension: Critical Role for Serotonin-Induced Smooth Muscle Hyperplasia Circulation, April 18, 2006; 113(15): 1857 - 1864. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sturrock, B. Cahill, K. Norman, T. P. Huecksteadt, K. Hill, K. Sanders, S. V. Karwande, J. C. Stringham, D. A. Bull, M. Gleich, et al. Transforming growth factor-beta1 induces Nox4 NAD(P)H oxidase and reactive oxygen species-dependent proliferation in human pulmonary artery smooth muscle cells Am J Physiol Lung Cell Mol Physiol, April 1, 2006; 290(4): L661 - L673. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Takahashi, N. Goto, Y. Kojima, Y. Tsuda, Y. Morio, M. Muramatsu, and Y. Fukuchi Downregulation of type II bone morphogenetic protein receptor in hypoxic pulmonary hypertension Am J Physiol Lung Cell Mol Physiol, March 1, 2006; 290(3): L450 - L458. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. D. Michelakis Spatio-Temporal Diversity of Apoptosis Within the Vascular Wall in Pulmonary Arterial Hypertension: Heterogeneous BMP Signaling May Have Therapeutic Implications Circ. Res., February 3, 2006; 98(2): 172 - 175. [Full Text] [PDF]
|
|
|
|
|
|
K. Teichert-Kuliszewska, M. J.B. Kutryk, M. A. Kuliszewski, G. Karoubi, D. W. Courtman, L. Zucco, J. Granton, and D. J. Stewart Bone Morphogenetic Protein Receptor-2 Signaling Promotes Pulmonary Arterial Endothelial Cell Survival: Implications for Loss-of-Function Mutations in the Pathogenesis of Pulmonary Hypertension Circ. Res., February 3, 2006; 98(2): 209 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Caldwell, R. Gadipatti, K. B. Lane, and V. L. Shepherd HIV-1 TAT represses transcription of the bone morphogenic protein receptor-2 in U937 monocytic cells J. Leukoc. Biol., January 1, 2006; 79(1): 192 - 201. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Rondelet, F. Kerbaul, R. Van Beneden, I. Hubloue, S. Huez, P. Fesler, M. Remmelink, S. Brimioulle, I. Salmon, and R. Naeije Prevention of pulmonary vascular remodeling and of decreased BMPR-2 expression by losartan therapy in shunt-induced pulmonary hypertension Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2319 - H2324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. B. Frank, A. Abtahi, D.J. Yamaguchi, S. Manning, Y. Shyr, A. Pozzi, H. S. Baldwin, J. E. Johnson, and M. P. de Caestecker Bone Morphogenetic Protein 4 Promotes Pulmonary Vascular Remodeling in Hypoxic Pulmonary Hypertension Circ. Res., September 2, 2005; 97(5): 496 - 504. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Stewart Bone Morphogenetic Protein Receptor-2 and Pulmonary Arterial Hypertension: Unraveling a Riddle Inside an Enigma? Circ. Res., May 27, 2005; 96(10): 1033 - 1035. [Full Text] [PDF]
|
|
|
|
|
|
X. Yang, L. Long, M. Southwood, N. Rudarakanchana, P. D. Upton, T. K. Jeffery, C. Atkinson, H. Chen, R. C. Trembath, and N. W. Morrell Dysfunctional Smad Signaling Contributes to Abnormal Smooth Muscle Cell Proliferation in Familial Pulmonary Arterial Hypertension Circ. Res., May 27, 2005; 96(10): 1053 - 1063. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. D. Zhao, D. W. Courtman, Y. Deng, L. Kugathasan, Q. Zhang, and D. J. Stewart Rescue of Monocrotaline-Induced Pulmonary Arterial Hypertension Using Bone Marrow-Derived Endothelial-Like Progenitor Cells: Efficacy of Combined Cell and eNOS Gene Therapy in Established Disease Circ. Res., March 4, 2005; 96(4): 442 - 450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. X.-J. Yuan and L. J. Rubin Pathogenesis of Pulmonary Arterial Hypertension: The Need for Multiple Hits Circulation, February 8, 2005; 111(5): 534 - 538. [Full Text] [PDF]
|
|
|
|
|
|
T. K. Jeffery, P. D. Upton, R. C. Trembath, and N. W. Morrell BMP4 inhibits proliferation and promotes myocyte differentiation of lung fibroblasts via Smad1 and JNK pathways Am J Physiol Lung Cell Mol Physiol, February 1, 2005; 288(2): L370 - L378. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Beppu, F. Ichinose, N. Kawai, R. C. Jones, P. B. Yu, W. M. Zapol, K. Miyazono, E. Li, and K. D. Bloch 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, December 1, 2004; 287(6): L1241 - L1247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K. K. Sheares, T. K. Jeffery, L. Long, X. Yang, and N. W. Morrell Differential effects of TGF-{beta}1 and BMP-4 on the hypoxic induction of cyclooxygenase-2 in human pulmonary artery smooth muscle cells Am J Physiol Lung Cell Mol Physiol, November 1, 2004; 287(5): L919 - L927. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. McMurtry, S. Bonnet, X. Wu, J. R.B. Dyck, A. Haromy, K. Hashimoto, and E. D. Michelakis Dichloroacetate Prevents and Reverses Pulmonary Hypertension by Inducing Pulmonary Artery Smooth Muscle Cell Apoptosis Circ. Res., October 15, 2004; 95(8): 830 - 840. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Takeda, F. Otsuka, K. Nakamura, K. Inagaki, J. Suzuki, D. Miura, H. Fujio, H. Matsubara, H. Date, T. Ohe, et al. 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, September 1, 2004; 145(9): 4344 - 4354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Newman, B. L. Fanburg, S. L. Archer, D. B. Badesch, R. J. Barst, J. G.N. Garcia, P. N. Kao, J. A. Knowles, J. E. Loyd, M. D. McGoon, et al. Pulmonary Arterial Hypertension: Future Directions: Report of a National Heart, Lung and Blood Institute/Office of Rare Diseases Workshop Circulation, June 22, 2004; 109(24): 2947 - 2952. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Humbert, N. W. Morrell, S. L. Archer, K. R. Stenmark, M. R. MacLean, I. M. Lang, B. W. Christman, E. K. Weir, O. Eickelberg, N. F. Voelkel, et al. Cellular and molecular pathobiology of pulmonary arterial hypertension J. Am. Coll. Cardiol., June 16, 2004; 43(12_Suppl_S): 13S - 24S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Newman, R. C. Trembath, J. A. Morse, E. Grunig, J. E. Loyd, S. Adnot, F. Coccolo, C. Ventura, J. A. Phillips III, J. A. Knowles, et al. Genetic basis of pulmonary arterial hypertension: Current understanding and future directions J. Am. Coll. Cardiol., June 16, 2004; 43(12_Suppl_S): 33S - 39S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Chaouat, F Coulet, C Favre, G Simonneau, E Weitzenblum, F Soubrier, and M Humbert Endoglin germline mutation in a patient with hereditary haemorrhagic telangiectasia and dexfenfluramine associated pulmonary arterial hypertension Thorax, May 1, 2004; 59(5): 446 - 448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rabinovitch The Mouse Through the Looking Glass: A New Door Into the Pathophysiology of Pulmonary Hypertension Circ. Res., April 30, 2004; 94(8): 1001 - 1004. [Full Text] [PDF]
|
|
|
|
|
|
J. West, K. Fagan, W. Steudel, B. Fouty, K. Lane, J. Harral, M. Hoedt-Miller, Y. Tada, J. Ozimek, R. Tuder, et al. Pulmonary Hypertension in Transgenic Mice Expressing a Dominant-Negative BMPRII Gene in Smooth Muscle Circ. Res., April 30, 2004; 94(8): 1109 - 1114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|