| 1. | Simonneau G, Robbins IM, Beghetti M, Channick RN, Delcroix M, Denton CP, Elliott CG, Gaine SP, Gladwin MT, Jing ZC, et al.. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2009;54:S43–S54. |
| 2. | Lane KB, Machado RD, Pauciulo M, Thomson JR, Phillips JA, Loyd JE, Nichols WC, Trembath RC; The International PPH Consortium. Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. Nat Genet 2000;26:81–84. |
| 3. | Deng Z, Morse JH, Slager SL, Cuervo N, Moore KJ, Venetos G, Kalachikov S, Cayanis E, Fischer SG, Barst RJ, et al.. 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. |
| 4. | Machado RD, Aldred MA, James V, Harrison RE, Patel B, Schwalbe EC, Gruenig E, Janssen B, Koehler R, Seeger W, et al.. Mutations of the TGF-beta type II receptor BMPR2 in pulmonary arterial hypertension. Hum Mutat 2006;27:121–132. |
| 5. | Aldred MA, Vijayakrishnan J, James V, Soubrier F, Gomez-Sanchez MA, Martensson G, Galie N, Manes A, Corris P, Simonneau G, et al.. BMPR2 gene rearrangements account for a significant proportion of mutations in familial and idiopathic pulmonary arterial hypertension. Hum Mutat 2006;27:212–213. |
| 6. | Shintani M, Yagi H, Nakayama T, Saji T, Matsuoka R. A new nonsense mutation of SMAD8 associated with pulmonary arterial hypertension. J Med Genet 2009;46:331–337. |
| 7. | Davis BN, Hilyard AC, Lagna G, Hata A. Smad proteins control drosha-mediated microRNA maturation. Nature 2008;454:56–61. |
| 8. | Davis BN, Hilyard AC, Nguyen PH, Lagna G, Hata A. Smad proteins bind a conserved RNA sequence to promote microRNA maturation by drosha. Mol Cell 2010;39:373–384. |
| 9. | Drake KM, Comhair SA, Erzurum SC, Aldred MA. MicroRNA processing is dysregulated by mutations associated with pulmonary arterial hypertension. Proc Am Thorac Soc 2011;8:205. |
| 10. | Drake KM, Comhair SAA, Erzurum SC, Aldred MA. Dysregulated microRNA processing in pulmonary arterial hypertension contributes to endothelial and smooth muscle cell hyperproliferation. Am J Respir Crit Care Med 2011;183:A2523. |
| 11. | Masri FA, Xu W, Comhair SA, Asosingh K, Koo M, Vasanji A, Drazba J, Anand-Apte B, Erzurum SC. Hyperproliferative apoptosis-resistant endothelial cells in idiopathic pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol 2007;293:L548–L554. |
| 12. | Xu W, Koeck T, Lara AR, Neumann D, DiFilippo FP, Koo M, Janocha AJ, Masri FA, Arroliga AC, Jennings C, et al.. Alterations of cellular bioenergetics in pulmonary artery endothelial cells. Proc Natl Acad Sci USA 2007;104:1342–1347. |
| 13. | Aytekin M, Comhair SA, de la Motte C, Bandyopadhyay SK, Farver CF, Hascall VC, Erzurum SC, Dweik RA. High levels of hyaluronan in idiopathic pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol 2008;295:L789–L799. |
| 14. | Asosingh K, Aldred MA, Vasanji A, Drazba J, Sharp J, Farver C, Comhair SA, Xu W, Licina L, Huang L, et al.. Circulating angiogenic precursors in idiopathic pulmonary arterial hypertension. Am J Pathol 2008;172:615–627. |
| 15. | Aldred MA, Comhair SA, Varella-Garcia M, Asosingh K, Xu W, Noon GP, Thistlethwaite PA, Tuder RM, Erzurum SC, Geraci MW, et al.. Somatic chromosome abnormalities in the lungs of patients with pulmonary arterial hypertension. Am J Respir Crit Care Med 2010;182:1153–1160. |
| 16. | Upton PD, Davies RJ, Trembath RC, Morrell NW. Bone morphogenetic protein (BMP) and activin type II receptors balance BMP9 signals mediated by activin receptor-like kinase-1 in human pulmonary artery endothelial cells. J Biol Chem 2009;284:15794–15804. |
| 17. | Wang B, Hsu SH, Majumder S, Kutay H, Huang W, Jacob ST, Ghoshal K. TGFbeta-mediated upregulation of hepatic miR-181b promotes hepatocarcinogenesis by targeting TIMP3. Oncogene 2010;29:1787–1797. |
| 18. | 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. |
| 19. | Trembath RC, Thomson JR, Machado RD, Morgan NV, Atkinson C, Winship I, Simonneau G, Galie N, Loyd JE, Humbert M, et al.. Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia. N Engl J Med 2001;345:325–334. |
| 20. | 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. |
| 21. | Mache CJ, Gamillscheg A, Popper HH, Haworth SG. Early-life pulmonary arterial hypertension with subsequent development of diffuse pulmonary arteriovenous malformations in hereditary haemorrhagic telangiectasia type 1. Thorax 2008;63:85–86. |
| 22. | 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. |
| 23. | Takahashi H, Goto N, Kojima Y, Tsuda Y, Morio Y, Muramatsu M, Fukuchi Y. Downregulation of type II bone morphogenetic protein receptor in hypoxic pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 2006;290:L450–L458. |
| 24. | Morty RE, Nejman B, Kwapiszewska G, Hecker M, Zakrzewicz A, Kouri FM, Peters DM, Dumitrascu R, Seeger W, Knaus P, et al.. Dysregulated bone morphogenetic protein signaling in monocrotaline-induced pulmonary arterial hypertension. Arterioscler Thromb Vasc Biol 2007;27:1072–1078. |
| 25. | Ramos MF, Lame MW, Segall HJ, Wilson DW. Smad signaling in the rat model of monocrotaline pulmonary hypertension. Toxicol Pathol 2008;36:311–320. |
| 26. | Orvis GD, Jamin SP, Kwan KM, Mishina Y, Kaartinen VM, Huang S, Roberts AB, Umans L, Huylebroeck D, Zwijsen A, et al.. Functional redundancy of TGF-beta family type I receptors and receptor-Smads in mediating anti-mullerian hormone-induced mullerian duct regression in the mouse. Biol Reprod 2008;78:994–1001. |
| 27. | Lechleider RJ, Ryan JL, Garrett L, Eng C, Deng C, Wynshaw-Boris A, Roberts AB. Targeted mutagenesis of Smad1 reveals an essential role in chorioallantoic fusion. Dev Biol 2001;240:157–167. |
| 28. | Tremblay KD, Dunn NR, Robertson EJ. Mouse embryos lacking Smad1 signals display defects in extra-embryonic tissues and germ cell formation. Development 2001;128:3609–3621. |
| 29. | Chang H, Huylebroeck D, Verschueren K, Guo Q, Matzuk MM, Zwijsen A. Smad5 knockout mice die at mid-gestation due to multiple embryonic and extraembryonic defects. Development 1999;126:1631–1642. |
| 30. | Huang Z, Wang D, Ihida-Stansbury K, Jones PL, Martin JF. Defective pulmonary vascular remodeling in Smad8 mutant mice. Hum Mol Genet 2009;18:2791–2801. |
| 31. | Howe JR, Roth S, Ringold JC, Summers RW, Jarvinen HJ, Sistonen P, Tomlinson IP, Houlston RS, Bevan S, Mitros FA, et al.. Mutations in the SMAD4/DPC4 gene in juvenile polyposis. Science 1998;280:1086–1088. |
| 32. | Hamid R, Cogan JD, Hedges LK, Austin E, Phillips JA, Newman JH, Loyd JE. Penetrance of pulmonary arterial hypertension is modulated by the expression of normal BMPR2 allele. Hum Mutat 2009;30:649–654. |
| 33. | Caruso P, MacLean MR, Khanin R, McClure J, Soon E, Southgate M, MacDonald RA, Greig JA, Robertson KE, Masson R, et al.. Dynamic changes in lung microRNA profiles during the development of pulmonary hypertension due to chronic hypoxia and monocrotaline. Arterioscler Thromb Vasc Biol 2010;30:716–723. |
| 34. | Long L, Crosby A, Yang X, Southwood M, Upton PD, Kim DK, Morrell NW. Altered bone morphogenetic protein and transforming growth factor-beta signaling in rat models of pulmonary hypertension: potential for activin receptor-like kinase-5 inhibition in prevention and progression of disease. Circulation 2009;119:566–576. |
| 35. | Krichevsky AM, Gabriely G. miR-21: a small multi-faceted MA. J Cell Mol Med 2009;13:39–53. |
| 36. | Selcuklu SD, Donoghue MT, Spillane C. miR-21 as a key regulator of oncogenic processes. Biochem Soc Trans 2009;37:918–925. |
| 37. | Liu G, Friggeri A, Yang Y, Milosevic J, Ding Q, Thannickal VJ, Kaminski N, Abraham E. miR-21 mediates fibrogenic activation of pulmonary fibroblasts and lung fibrosis. J Exp Med 2010;207:1589–1597. |
| 38. | Nasim MT, Ghouri A, Patel B, James V, Rudarakanchana N, Morrell NW, Trembath RC. Stoichiometric imbalance in the receptor complex contributes to dysfunctional BMPR-II mediated signalling in pulmonary arterial hypertension. Hum Mol Genet 2008;17:1683–1694. |
| 39. | Sui X, Li D, Qiu H, Gaussin V, Depre C. Activation of the bone morphogenetic protein receptor by h11kinase/HSP22 promotes cardiac cell growth and survival. Circ Res 2009;104:887–895. |
