Bone morphogenetic protein receptor-2 signaling promotes pulmonary arterial endothelial cell survival: Implications for loss-of-function mutations in the pathogenesis of pulmonary hypertension

Circulation Research

Volumn 98, Issue 2, 2006, Pages 209-217

  Teichert Kuliszewska, Krystyna ^a   Kutryk, Michael J B ^a,c,d   Kuliszewski, Michael A ^a   Karoubi, Golnaz ^a,c   Courtman, David W ^a,c   Zucco, Liana ^a   Granton, John ^b,c   Stewart, Duncan J ^a,c,d,e  

^a ST MICHAEL'S HOSPITAL   (Canada)

^b UNIVERSITY HEALTH NETWORK   (Canada)

^c UNIVERSITY OF TORONTO   (Canada)

^d UNIVERSITY OF TORONTO   (Canada)

^e Northern Therapeutics Inc   (Canada)

Author keywords

Apoptosis; Bone morphogenetic proteins; Bone morphogenetic receptor 2; Endothelial cells; Endothelial progenitor cells; Pulmonary arterial hypertension

Indexed keywords

BONE MORPHOGENETIC PROTEIN 2; CASPASE 3; LIPOCORTIN 5; OSTEOGENIC PROTEIN 1; SMALL INTERFERING RNA; TUMOR NECROSIS FACTOR ALPHA; BMP2 PROTEIN, HUMAN; BONE MORPHOGENETIC PROTEIN; BONE MORPHOGENETIC PROTEIN RECEPTOR 2; TRANSFORMING GROWTH FACTOR BETA;

ADULT; APOPTOSIS; ARTICLE; CELL SURVIVAL; CLINICAL ARTICLE; ENZYME ACTIVITY; FEMALE; FLOW CYTOMETRY; GENE SILENCING; HUMAN; HUMAN CELL; LUNG ENDOTHELIUM; MALE; MUTATION; PATHOGENESIS; PRIORITY JOURNAL; PULMONARY HYPERTENSION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SMOOTH MUSCLE FIBER; STEM CELL; WESTERN BLOTTING; AGED; CELL CULTURE; DRUG EFFECT; ENDOTHELIUM CELL; GENETICS; MIDDLE AGED; PATHOLOGY; PHYSIOLOGY; PULMONARY ARTERY; SIGNAL TRANSDUCTION;

ADULT; AGED; APOPTOSIS; BONE MORPHOGENETIC PROTEIN RECEPTORS, TYPE II; BONE MORPHOGENETIC PROTEINS; CELL SURVIVAL; CELLS, CULTURED; ENDOTHELIAL CELLS; FEMALE; HUMANS; HYPERTENSION, PULMONARY; MALE; MIDDLE AGED; MUTATION; PULMONARY ARTERY; SIGNAL TRANSDUCTION; STEM CELLS; TRANSFORMING GROWTH FACTOR BETA;

EID: 33644865928     PISSN: 00097330     EISSN: None     Source Type: Journal    
DOI: 10.1161/01.RES.0000200180.01710.e6     Document Type: Article

References (40)

1. Rubin LJ. Primary pulmonary hypertension. N Engl J Med. 1997;336: 111-117.
2. Yi ES, Kim H, Ahn H, Strother J, Morris T, Masliah E, Hansen LA, Park K, Friedman PJ. Distribution of obstructive intimal lesions and their cellular phenotypes in chronic pulmonary hypertension. A morphometric and immunohistochemical study. Am J Respir Crit Care Med. 2000;162:1577-1586.
3. Cool CD, Stewart JS, Werahera P, Miller GJ, Williams RL, Voelkel NF, Tuder RM. Three-dimensional reconstruction of pulmonary arteries in plexiform pulmonary hypertension using cell-specific markers. Evidence for a dynamic and heterogeneous process of pulmonary endothelial cell growth. Am J Pathol. 1999;155:411-419.
4. Taraseviciene-Stewart L, Kasahara Y, Alger L, Hirth P, Mc MG, Waltenberger J, Voelkel NF, Tuder RM. Inhibition of the VEGF receptor 2 combined with chronic hypoxia causes cell death-dependent pulmonary endothelial cell proliferation and severe pulmonary hypertension. FASEB J. 2001;15:427-438.
5. Campbell AI, Zhao Y, Sandhu R, Stewart DJ. Cell-based gene transfer of vascular endothelial growth factor attenuates monocrotaline-induced pulmonary hypertension. Circulation. 2001;104:2242-2248.
6. Zhao YD, Campbell AI, Robb M, Ng D, Stewart DJ. Protective role of angiopoietin-1 in experimental pulmonary hypertension. Circ Res. 2003;92: 984-991.
7. Nichols WC, Koller DL, Slovis B, Foroud T, Terry VH, Arnold ND, Siemieniak DR, Wheeler L, Phillips JA III, Newman JH, Conneally PM, Ginsburg D, Loyd JE. Localization of the gene for familial primary pulmonary hypertension to chromosome 2q31-32. Nat Genet. 1997;15: 277-280.
8. Lane KB, Machado RD, Pauciulo MW, Thomson JR, Phillips JA III, Loyd JE, Nichols WC, Trembath RC. Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. The International PPH Consortium. Nat Genet. 2000;26:81-84.
9. Thomson JR, Machado RD, Pauciulo MW, Morgan NV, Humbert M, Elliott GC, Ward K, Yacoub M, Mikhail G, Rogers P, Newman J, Wheeler L, Higenbottam T, Gibbs JS, Egan J, Crazier A, Peacock A, Allcock R, Corris P, Loyd JE, Trembath RC, Nichols WC. Sporadic primary pulmonary hypertension is associated with germline mutations of the gene encoding BMPR-II, a receptor member of the TGF-beta family. J Med Genet. 2000;37:741-745.
10. Machado RD, Pauciulo MW, Thomson JR, Lane KB, Morgan NV, Wheeler L, Phillips JA III, 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. 2001;68:92-102.
11. Deng Z, Morse JH, Slager SL, Cuervo N, Moore KJ, Venetos G, Kalachikov S, Cayanis E, Fischer SG, Barst RJ, Hodge SE, Knowles JA. Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene. Am J Hum Genet. 2000;67:737-744.
12. Yokouchi Y, Sakiyama J, Kameda T, Iba H, Suzuki A, Ueno N, Kuroiwa A. BMP-2/-4 mediate programmed cell death in chicken limb buds. Development. 1996;122:3725-3734.
13. Iwasaki S, Iguchi M, Watanabe K, Hoshino R, Tsujimoto M, Kohno M. Specific activation of the p38 mitogen-activated protein kinase signaling pathway and induction of neurite outgrowth in PC12 cells by bone morphogenetic protein-2. J Biol Chem. 1999;274:26503-26510.
14. Bhatia M, Bonnet D, Wu D, Murdoch B, Wrana J, Gallacher L, Dick JE. Bone morphogenetic proteins regulate the developmental program of human hematopoietic stem cells. J Exp Med. 1999;189:1139-1148.
15. 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. 2003;285:L740-L754.
16. 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. 2001;104:790-795.
17. Izumi M, Fujio Y, Kunisada K, Negoro S, Tone E, Funamoto M, Osugi T, Oshima Y, Nakaoka Y, Kishimoto T, Yamauchi-Takihara K, Hirota H. Bone morphogenetic protein-2 inhibits serum deprivation-induced apoptosis of neonatal cardiac myocytes through activation of the Smad1 pathway. J Biol Chem. 2001;276:31133-31141.
18. Shin I, Bakin AV, Rodeck U, Brunet A, Arteaga CL. Transforming growth factor beta enhances epithelial cell survival via Akt-dependent regulation of FKHRL1. Mol Biol Cell. 2001;12:3328-3339.
19. Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature. 2001;411:494-498.
20. Elbashir SM, Lendeckel W, Tuschl T. RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes Dev. 2001;15:188-200.
21. Asahara T, Murohara T, Sullivan A, Silver M, van der ZR, Li T, Witzenbichler B, Schatteman G, Isner JM. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275:964-967.
22. Taraseviciene-Stewart L, Gera L, Hirth P, Voelkel NF, Tuder RM, Stewart JM. A bradykinin antagonist and a caspase inhibitor prevent severe pulmonary hypertension in a rat model. Can J Physiol Pharmacol. 2002;80:269-274.
23. Machado RD, James V, Southwood M, Harrison RE, Atkinson C, Stewart S, Morrell NW, Trembath RC, Aldred MA. Investigation of second genetic hits at the BMPR2 locus as a modulator of disease progression in familial pulmonary arterial hypertension. Circulation. 2005;111: 607-613.
24. Harrison RE, Berger R, Haworth SG, Tulloh R, Mache CJ, Morrell NW, Aldred MA, Trembath RC. Transforming growth factor-beta receptor mutations and pulmonary arterial hypertension in childhood. Circulation. 2005;111:435-441.
25. De Caestecker M, Meyrick B. Bone morphogenetic proteins, genetics and the pathophysiology of primary pulmonary hypertension. Respir Res. 2001;2:193-197.
26. Atkinson C, Stewart S, Upton PD, Machado R, Thomson JR, Trembath RC, Morrell NW. Primary pulmonary hypertension is associated with reduced pulmonary vascular expression of type II bone morphogenetic protein receptor. Circulation. 2002;105:1672-1678.
27. Richter A, Yeager ME, Zaiman A, Cool CD, Voelkel NF, Tuder RM. Impaired transforming growth factor-beta signaling in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med. 2004;170: 1340-1348.
28. Abdalla SA, Gallione CJ, Barst RJ, Horn EM, Knowles JA, Marchuk DA, Letarte M, Morse JH. Primary pulmonary hypertension in families with hereditary haemorrhagic telangiectasia. Eur Respir J. 2004;23:373-377.
29. Abdalla SA, Cymerman U, Johnson RM, Deber CM, Letarte M. Disease-associated mutations in conserved residues of ALK-1 kinase domain. Eur J Hum Genet. 2003;11:279-287.
30. Cymerman U, Vera S, Karabegovic A, Abdalla S, Letarte M. Characterization of 17 novel endoglin mutations associated with hereditary hemorrhagic telangiectasia. Hum Mutat. 2003;21:482-492.
31. Luttun A, Carmeliet G, Carmeliet P. Vascular progenitors: from biology to treatment. Trends Cardiovasc Med. 2002;12:88-96.
32. Schachinger V, Assmus B, Britten MB, Honold J, Lehmann R, Teupe C, Abolmaali ND, Vogl TJ, Hofmann WK, Martin H, Dimmeler S, Zeiher AM. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI Trial. J Am Coll Cardiol. 2004;44:1690-1699.
33. Urbich C, Dimmeler S. Endothelial progenitor cells: characterization and role in vascular biology. Circ Res. 2004;95:343-353.
34. Dimmeler S, Zeiher AM. Vascular repair by circulating endothelial progenitor cells: the missing link in atherosclerosis? J Mol Med. 2004;82: 671-677.
35. Morse JH, Deng Z, Knowles JA. Genetic aspects of pulmonary arterial hypertension. Ann Med. 2001;33:596-603.
36. 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. 2005;96: 1053-1063.
37. Stewart DJ. Bone morphogenetic protein receptor-2 and pulmonary arterial hypertension: unraveling a riddle inside an enigma? Circ Res. 2005; 96:1033-1035.
38. Zhao YD, Courtman DW, Deng Y, Kugathasan L, Zhang Q, Stewart DJ. 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. 2005;96:442-450.
39. Voelkel NF, Cool C, Taraceviene-Stewart L, Geraci MW, Yeager M, Bull T, Kasper M, Tuder RM. Janus face of vascular endothelial growth factor: the obligatory survival factor for lung vascular endothelium controls precapillary artery remodeling in severe pulmonary hypertension. Crit Care Med. 2002;30:S251-S256.
40. Eddahibi S, Humbert M, Fadel E, Raffestin B, Darmon M, Capron F, Simonneau G, Dartevelle P, Hamon M, Adnot S. Serotonin transporter overexpression is responsible for pulmonary artery smooth muscle hyperplasia in primary pulmonary hypertension. J Clin Invest. 2001;108: 1141-1150.