Bone morphogenetic protein receptor type 2 mutation in pulmonary arterial hypertension: A view on the right ventricle

Circulation

Volumn 133, Issue 18, 2016, Pages 1747-1760

  Van Der Bruggen, Cathelijne E ^a   Happé, Chris M ^a   Dorfmüller, Peter ^b,c,d   Trip, Pia ^a   Spruijt, Onno A ^a   Rol, Nina ^a   Hoevenaars, Femke P ^a   Houweling, Arjan C ^e   Girerd, Barbara ^b,c,d   Marcus, Johannes T ^e   Mercier, Olaf ^d   Humbert, Marc ^b,c,d   Handoko, M Louis ^a   Van Der Velden, Jolanda ^a   Vonk Noordegraaf, Anton ^a   Bogaard, Harm Jan ^a   Goumans, Marie José ^f   De Man, Frances S ^a  

^a VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^b UNIVERSITÉ PARIS SACLAY   (France)

^c BICÊTRE HOSPITAL   (France)

^d CENTRE CHIRURGICAL MARIE LANNELONGUE   (France)

^e VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^f LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

genetics; heart failure; hypertension, pulmonary

Indexed keywords

ATRIAL NATRIURETIC FACTOR; BONE MORPHOGENETIC PROTEIN RECEPTOR 2; CARNITINE PALMITOYLTRANSFERASE I; CARNITINE PALMITOYLTRANSFERASE IB; CD36 ANTIGEN; FATTY ACID BINDING PROTEIN; FATTY ACID BINDING PROTEIN 3; GLUCOSE TRANSPORTER 1; HEXOKINASE; HEXOKINASE 1; HEXOKINASE 2; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG; BMPR2 PROTEIN, HUMAN;

ADULT; APOPTOSIS; ARTICLE; CAPILLARY DENSITY; CARDIOVASCULAR MAGNETIC RESONANCE; CONTROLLED STUDY; FEMALE; GENE MUTATION; GENETIC ANALYSIS; HEART CATHETERIZATION; HEART HYPERTROPHY; HEART INDEX; HEART MUSCLE FIBROSIS; HEART MUSCLE METABOLISM; HEART RIGHT VENTRICLE EJECTION FRACTION; HEART RIGHT VENTRICLE FUNCTION; HETEROZYGOTE; HISTOLOGY; HUMAN; IN VIVO STUDY; INFLAMMATION; LUNG ARTERY PRESSURE; LUNG VASCULAR RESISTANCE; MAJOR CLINICAL STUDY; MALE; PRIORITY JOURNAL; PULMONARY HYPERTENSION; SIGNAL TRANSDUCTION; AGED; GENETICS; HYPERTENSION, PULMONARY; MIDDLE AGED; MUTATION; RETROSPECTIVE STUDY;

ADULT; AGED; BONE MORPHOGENETIC PROTEIN RECEPTORS, TYPE II; FEMALE; HUMANS; HYPERTENSION, PULMONARY; MALE; MIDDLE AGED; MUTATION; RETROSPECTIVE STUDIES; VENTRICULAR DYSFUNCTION, RIGHT; VENTRICULAR FUNCTION, RIGHT;

EID: 84961223811     PISSN: 00097322     EISSN: 15244539     Source Type: Journal    
DOI: 10.1161/CIRCULATIONAHA.115.020696     Document Type: Article

References (42)

1. Humbert M, Sitbon O, Chaouat A, Bertocchi M, Habib G, Gressin V, Yaïci A, Weitzenblum E, Cordier JF, Chabot F, Dromer C, Pison C, Reynaud-Gaubert M, Haloun A, Laurent M, Hachulla E, Cottin V, Degano B, Jaïs X, Montani D, Souza R, Simonneau G., Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation 2010 122 156 163. doi: 10.1161/CIRCULATIONAHA.109.911818.
2. Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A, Gomez Sanchez MA, Krishna Kumar R, Landzberg M, Machado RF, Olschewski H, Robbins IM, Souza R., Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2013 62 25 suppl D34 D41. doi: 10.1016/j.jacc.2013.10.029.
3. Runo JR, Loyd JE., Primary pulmonary hypertension. Lancet 2003 361 1533 1544. doi: 10.1016/S0140-6736(03)13167-4.
4. van de Veerdonk MC, Kind T, Marcus JT, Mauritz G-J, Heymans MW, Bogaard H-J, Boonstra A, Marques KMJ, Westerhof N, Vonk-Noordegraaf A., Progressive right ventricular dysfunction in patients with pulmonary arterial hypertension responding to therapy. J Am Coll Cardiol 2011 58 2511 2519
5. Cogan JD, Pauciulo MW, Batchman AP, Prince MA, Robbins IM, Hedges LK, Stanton KC, Wheeler LA, Phillips JA 3rd, Loyd JE, Nichols WC., High frequency of BMPR2 exonic deletions/duplications in familial pulmonary arterial hypertension. Am J Respir Crit Care Med 2006 174 590 598. doi: 10.1164/rccm.200602-165OC.
6. 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. doi: 10.1086/303059.
7. Lane KB, Machado RD, Pauciulo MW, Thomson JR, Phillips JA, Loyd JE, Nichols WC, Trembath RC., International PPH Consortium Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. Nat Genet 2000 26 81 84
8. Newman JH, Wheeler L, Lane KB, Loyd E, Gaddipati R, Phillips JA 3rd, Loyd JE., Mutation in the gene for bone morphogenetic protein receptor II as a cause of primary pulmonary hypertension in a large kindred. N Engl J Med 2001 345 319 324. doi: 10.1056/NEJM200108023450502.
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, Crozier 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. Soubrier F, Chung WK, Machado R, Grünig E, Aldred M, Geraci M, Loyd JE, Elliott CG, Trembath RC, Newman JH, Humbert M., Genetics and genomics of pulmonary arterial hypertension. J Am Coll Cardiol 2013 62 25 suppl D13 D21. doi: 10.1016/j.jacc.2013.10.035.
11. Machado RD, Eickelberg O, Elliott CG, Geraci MW, Hanaoka M, Loyd JE, Newman JH, Phillips JA 3rd, Soubrier F, Trembath RC, Chung WK., Genetics and genomics of pulmonary arterial hypertension. J Am Coll Cardiol 2009 54 1 Suppl S32 S42. doi: 10.1016/j.jacc.2009.04.015.
12. Girerd B, Montani D, Eyries M, Yaici A, Sztrymf B, Coulet F, Sitbon O, Simonneau G, Soubrier F, Humbert M., Absence of influence of gender and BMPR2 mutation type on clinical phenotypes of pulmonary arterial hypertension. Respir Res 2010 11 73. doi: 10.1186/1465-9921-11-73.
13. Rosenzweig EB, Morse JH, Knowles JA, Chada KK, Khan AM, Roberts KE, McElroy JJ, Juskiw NK, Mallory NC, Rich S, Diamond B, Barst RJ., Clinical implications of determining BMPR2 mutation status in a large cohort of children and adults with pulmonary arterial hypertension. J Heart Lung Transplant 2008 27 668 674. doi: 10.1016/j.healun.2008.02.009.
14. Sztrymf B, Coulet F, Girerd B, Yaici A, Jais X, Sitbon O, Montani D, Souza R, Simonneau G, Soubrier F, Humbert M., Clinical outcomes of pulmonary arterial hypertension in carriers of BMPR2 mutation. Am J Respir Crit Care Med 2008 177 1377 1383. doi: 10.1164/rccm.200712-1807OC.
15. Larkin EK, Newman JH, Austin ED, Hemnes AR, Wheeler L, Robbins IM, West JD, Phillips JA 3rd, Hamid R, Loyd JE., Longitudinal analysis casts doubt on the presence of genetic anticipation in heritable pulmonary arterial hypertension. Am J Respir Crit Care Med 2012 186 892 896. doi: 10.1164/rccm.201205-0886OC.
16. 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
17. Akhurst RJ., TGF beta signaling in health and disease. Nat Genet 2004 36 790 792. doi: 10.1038/ng0804-790.
18. Machado RD, Pauciulo MW, Thomson JR, Lane KB, Morgan NV, Wheeler L, Phillips JA 3rd, Newman J, Williams D, Galiè 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
19. Morrell NW., Pulmonary hypertension due to BMPR2 mutation: a new paradigm for tissue remodeling? Proc Am Thorac Soc 2006 3 680 686. doi: 10.1513/pats.200605-118SF.
20. Stacher E, Graham BB, Hunt JM, Gandjeva A, Groshong SD, McLaughlin VV, Jessup M, Grizzle WE, Aldred MA, Cool CD, Tuder RM., Modern age pathology of pulmonary arterial hypertension. Am J Respir Crit Care Med 2012 186 261 272. doi: 10.1164/rccm.201201-0164OC.
21. Dobaczewski M, Chen W, Frangogiannis NG., Transforming growth factor (TGF)-β signaling in cardiac remodeling. J Mol Cell Cardiol 2011 51 600 606. doi: 10.1016/j.yjmcc.2010.10.033.
22. Koitabashi N, Danner T, Zaiman AL, Pinto YM, Rowell J, Mankowski J, Zhang D, Nakamura T, Takimoto E, Kass DA., Pivotal role of cardiomyocyte TGF-β signaling in the murine pathological response to sustained pressure overload. J Clin Invest 2011 121 2301 2312. doi: 10.1172/JCI44824.
23. Rosenkranz S., TGF-beta1 and angiotensin networking in cardiac remodeling. Cardiovasc Res 2004 63 423 432. doi: 10.1016/j.cardiores.2004.04.030.
24. Hemnes AR, Brittain EL, Trammell AW, Fessel JP, Austin ED, Penner N, Maynard KB, Gleaves L, Talati M, Absi T, Disalvo T, West J., Evidence for right ventricular lipotoxicity in heritable pulmonary arterial hypertension. Am J Respir Crit Care Med 2014 189 325 334. doi: 10.1164/rccm.201306-1086OC.
25. Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Vonk Noordegraaf A, Beghetti M, Ghofrani A, Gomez Sanchez MA, Hansmann G, Klepetko W, Lancellotti P, Matucci M, McDonagh T, Pierard LA, Trindade PT, Zompatori M, Hoeper M., 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J 2015 46 903 975. doi: 10.1183/13993003.01032-2015.
26. Kabata H, Satoh T, Kataoka M, Tamura Y, Ono T, Yamamoto M, Huqun, Hagiwara K, Fukuda K, Betsuyaku T, Asano K., Bone morphogenetic protein receptor type 2 mutations, clinical phenotypes and outcomes of Japanese patients with sporadic or familial pulmonary hypertension. Respirology 2013 18 1076 1082. doi: 10.1111/resp.12117.
27. Brittain EL, Pugh ME, Wheeler LA, Robbins IM, Loyd JE, Newman JH, Larkin EK, Austin ED, Hemnes AR., Shorter survival in familial versus idiopathic pulmonary arterial hypertension is associated with hemodynamic markers of impaired right ventricular function. Pulm Circ 2013 3 589 598. doi: 10.1086/674326.
28. Evans JD, Girerd B, Montani D, Wang XJ, Galiè N, Austin ED, Elliott G, Asano K, Grünig E, Yan Y, Jing ZC, Manes A, Palazzini M, Wheeler LA, Nakayama I, Satoh T, Eichstaedt C, Hinderhofer K, Wolf M, Rosenzweig EB, Chung WK, Soubrier F, Simonneau G, Sitbon O, Gräf S, Kaptoge S, Di Angelantonio E, Humbert M, Morrell NW., BMPR2 mutations and survival in pulmonary arterial hypertension: an individual participant data meta-analysis. Lancet Respir Med 2016 4 129 137. doi: 10.1016/S2213-2600(15)00544-5.
29. Wolferen SA, van, Marcus JT, Boonstra A, Marques KMJ, Bronzwaer JGF, Spreeuwenberg MD, Postmus PE, Vonk-Noordegraaf A., Prognostic value of right ventricular mass, volume, and function in idiopathic pulmonary arterial hypertension. Eur Heart J 2007 28 1250 1257
30. Vonk-Noordegraaf A, Haddad F, Chin KM, Forfia PR, Kawut SM, Lumens J, Naeije R, Newman J, Oudiz RJ, Provencher S, Torbicki A, Voelkel NF, Hassoun PM., Right heart adaptation to pulmonary arterial hypertension: physiology and pathobiology. J Am Coll Cardiol 2013 62 25 suppl D22 D33. doi: 10.1016/j.jacc.2013.10.027.
31. Girerd B, Coulet F, Jaïs X, Eyries M, van der Bruggen C, De Man F, Houweling A, Dorfmüller P, Savale L, Sitbon O, Vonk-Noordegraaf A, Soubrier F, Simonneau G, Humbert M, Montani D., Characteristics of pulmonary arterial hypertension in affected carriers of a mutation located in the cytoplasmic tail of bone morphogenetic protein receptor type 2. Chest 2015 147 1385 1394. doi: 10.1378/chest.14-0880.
32. Xia Y, Lee K, Li N, Corbett D, Mendoza L, Frangogiannis NG., Characterization of the inflammatory and fibrotic response in a mouse model of cardiac pressure overload. Histochem Cell Biol 2009 131 471 481. doi: 10.1007/s00418-008-0541-5.
33. Koitabashi N, Danner T, Zaiman AL, Pinto YM, Rowell J, Mankowski J, Zhang D, Nakamura T, Takimoto E, Kass DA., Pivotal role of cardiomyocyte TGF-β signaling in the murine pathological response to sustained pressure overload. J Clin Invest 2011 121 2301 2312. doi: 10.1172/JCI44824.
34. Dobaczewski M, Chen W, Frangogiannis NG., Transforming growth factor (TGF)-β signaling in cardiac remodeling. J Mol Cell Cardiol 2011 51 600 606. doi: 10.1016/j.yjmcc.2010.10.033.
35. Rosenkranz S., TGF-beta1 and angiotensin networking in cardiac remodeling. Cardiovasc Res 2004 63 423 432. doi: 10.1016/j.cardiores.2004.04.030.
36. Akhurst RJ., TGF beta signaling in health and disease. Nat Genet 2004 36 790 792. doi: 10.1038/ng0804-790.
37. Voelkel NF, Quaife RA, Leinwand LA, Barst RJ, McGoon MD, Meldrum DR, Dupuis J, Long CS, Rubin LJ, Smart FW, Suzuki YJ, Gladwin M, Denholm EM, Gail DB, National Heart, Lung, and Blood Institute Working Group on Cellular and Molecular Mechanisms of Right Heart Failure Right ventricular function and failure: report of a National Heart, Lung, and Blood Institute working group on cellular and molecular mechanisms of right heart failure. Circulation 2006 114 1883 1891. doi: 10.1161/CIRCULATIONAHA.106.632208.
38. Rain S, Handoko ML, Vonk Noordegraaf A, Bogaard HJ, van der Velden J, de Man FS., Pressure-overload-induced right heart failure. Pflugers Arch 2014 466 1055 1063. doi: 10.1007/s00424-014-1450-1.
39. Megalou AJ, Glava C, Oikonomidis DL, Vilaeti A, Agelaki MG, Baltogiannis GG, Papalois A, Vlahos AP, Kolettis TM., Transforming growth factor-β inhibition attenuates pulmonary arterial hypertension in rats. Int J Clin Exp Med 2010 3 332 340
40. Piao L, Fang YH, Cadete VJ, Wietholt C, Urboniene D, Toth PT, Marsboom G, Zhang HJ, Haber I, Rehman J, Lopaschuk GD, Archer SL., The inhibition of pyruvate dehydrogenase kinase improves impaired cardiac function and electrical remodeling in two models of right ventricular hypertrophy: resuscitating the hibernating right ventricle. J Mol Med (Berl) 2010 88 47 60. doi: 10.1007/s00109-009-0524-6.
41. Fang YH, Piao L, Hong Z, Toth PT, Marsboom G, Bache-Wiig P, Rehman J, Archer SL., Therapeutic inhibition of fatty acid oxidation in right ventricular hypertrophy: exploiting Randle's cycle. J Mol Med (Berl) 2012 90 31 43. doi: 10.1007/s00109-011-0804-9.
42. Sutendra G, Dromparis P, Paulin R, Zervopoulos S, Haromy A, Nagendran J, Michelakis ED., A metabolic remodeling in right ventricular hypertrophy is associated with decreased angiogenesis and a transition from a compensated to a decompensated state in pulmonary hypertension. J Mol Med (Berl) 2013 91 1315 1327. doi: 10.1007/s00109-013-1059-4.