BMPR2 spruces up the endothelium in pulmonary hypertension

Protein and Cell

Volumn 6, Issue 10, 2015, Pages 703-708

  Xiong, Jianhua ^a  

^a NATIONAL HEART LUNG AND BLOOD INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

16ALPHA HYDROXYESTRONE; ALPHA CRYSTALLIN; BONE MORPHOGENETIC PROTEIN 9; BONE MORPHOGENETIC PROTEIN RECEPTOR 2; ENDOTHELIN 1; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; INTERLEUKIN 6; NAVARIXIN; TACROLIMUS; TRANSFORMING GROWTH FACTOR BETA; VASCULOTROPIN RECEPTOR;

ARTICLE; CAPILLARY ENDOTHELIAL CELL; ENDOTHELIAL DYSFUNCTION; ENDOTHELIUM; HEART DISEASE; HUMAN; INSULIN RESISTANCE; LUNG DISEASE; PRIORITY JOURNAL; PULMONARY HYPERTENSION; DRUG EFFECTS; HYPERTENSION, PULMONARY; METABOLISM; PATHOLOGY; SIGNAL TRANSDUCTION;

BONE MORPHOGENETIC PROTEIN RECEPTORS, TYPE II; ENDOTHELIUM; HYPERTENSION, PULMONARY; SIGNAL TRANSDUCTION;

EID: 84943347575     PISSN: 1674800X     EISSN: 16748018     Source Type: Journal    
DOI: 10.1007/s13238-015-0208-7     Document Type: Article

References (51)

1. Arciniegas E, Frid MG, Douglas IS, Stenmark KR (2007) Perspectives on endothelial-to-mesenchymal transition: potential contribution to vascular remodeling in chronic pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 293:L1–L8
2. Atkinson C, Stewart S, Upton PD, Machado R, Thomson JR, Trembath RC, Morrell NW (2002) Primary pulmonary hypertension is associated with reduced pulmonary vascular expression of type II bone morphogenetic protein receptor. Circulation 105:1672–1678
3. Austin ED, Loyd JE (2014) The genetics of pulmonary arterial hypertension. Circ Res 115:189–202
4. Austin ED, Cogan JD, West JD, Hedges LK, Hamid R, Dawson EP, Wheeler LA, Parl FF, Loyd JE, Phillips JA 3rd (2009) Alterations in oestrogen metabolism: implications for higher penetrance of familial pulmonary arterial hypertension in females. Eur Respir J 34:1093–1099
5. Austin ED, Hamid R, Hemnes AR, Loyd JE, Blackwell T, Yu C, Phillips Iii JA, Gaddipati R, Gladson S, Gu E et al (2012) BMPR2 expression is suppressed by signaling through the estrogen receptor. Biol Sex Differ 3:6
6. Brock M, Trenkmann M, Gay RE, Michel BA, Gay S, Fischler M, Ulrich S, Speich R, Huber LC (2009) Interleukin-6 modulates the expression of the bone morphogenic protein receptor type II through a novel STAT3-microRNA cluster 17/92 pathway. Circ Res 104:1184–1191
7. Burton VJ, Ciuclan LI, Holmes AM, Rodman DM, Walker C, Budd DC (2011a) Bone morphogenetic protein receptor II regulates pulmonary artery endothelial cell barrier function. Blood 117:333–341
8. Burton VJ, Holmes AM, Ciuclan LI, Robinson A, Roger JS, Jarai G, Pearce AC, Budd DC (2011b) Attenuation of leukocyte recruitment via CXCR1/2 inhibition stops the progression of PAH in mice with genetic ablation of endothelial BMPR-II. Blood 118:4750–4758
9. Ciumas M, Eyries M, Poirier O, Maugenre S, Dierick F, Gambaryan N, Montagne K, Nadaud S, Soubrier F (2013) Bone morphogenetic proteins protect pulmonary microvascular endothelial cells from apoptosis by upregulating alpha-B-crystallin. Arterioscler Thromb Vasc Biol 33:2577–2584
10. de Jesus Perez VA, Alastalo TP, Wu JC, Axelrod JD, Cooke JP, Amieva M, Rabinovitch M (2009) Bone morphogenetic protein 2 induces pulmonary angiogenesis via Wnt-beta-catenin and Wnt-RhoA-Rac1 pathways. J Cell Biol 184:83–99
11. Diebold I, Hennigs JK, Miyagawa K, Li CG, Nickel NP, Kaschwich M, Cao A, Wang L, Reddy S, Chen PI et al (2015) BMPR2 preserves mitochondrial function and DNA during reoxygenation to promote endothelial cell survival and reverse pulmonary hypertension. Cell Metab 21:596–608
12. Ferreira AJ, Shenoy V, Yamazato Y, Sriramula S, Francis J, Yuan L, Castellano RK, Ostrov DA, Oh SP, Katovich MJ et al (2009) Evidence for angiotensin-converting enzyme 2 as a therapeutic target for the prevention of pulmonary hypertension. Am J Respir Crit Care Med 179:1048–1054
13. Fessel JP, Loyd JE, Austin ED (2011) The genetics of pulmonary arterial hypertension in the post-BMPR2 era. Pulm Circ 1:305–319
14. Fessel JP, Hamid R, Wittmann BM, Robinson LJ, Blackwell T, Tada Y, Tanabe N, Tatsumi K, Hemnes AR, West JD (2012) Metabolomic analysis of bone morphogenetic protein receptor type 2 mutations in human pulmonary endothelium reveals widespread metabolic reprogramming. Pulm Circ 2:201–213
15. Foletta VC, Lim MA, Soosairajah J, Kelly AP, Stanley EG, Shannon M, He W, Das S, Massague J, Bernard O (2003) Direct signaling by the BMP type II receptor via the cytoskeletal regulator LIMK1. J Cell Biol 162:1089–1098
16. Frank DB, Lowery J, Anderson L, Brink M, Reese J, de Caestecker M (2008) 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:L98–109
17. Hong KH, Lee YJ, Lee E, Park SO, Han C, Beppu H, Li E, Raizada MK, Bloch KD, Oh SP (2008) Genetic ablation of the BMPR2 gene in pulmonary endothelium is sufficient to predispose to pulmonary arterial hypertension. Circulation 118:722–730
18. International PPHC, Lane KB, Machado RD, Pauciulo MW, Thomson JR, Phillips JA, Nichols WC, Trembath RC (2000) Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. Nat Genet 26:81–84
19. Johnson JA, Hemnes AR, Perrien DS, Schuster M, Robinson LJ, Gladson S, Loibner H, Bai S, Blackwell TR, Tada Y et al (2012) Cytoskeletal defects in Bmpr2-associated pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol 302:L474–L484
20. Kovacs G, Berghold A, Scheidl S, Olschewski H (2009) Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review. Eur Respir J 34:888–894
21. Lane KL, Talati M, Austin E, Hemnes AR, Johnson JA, Fessel JP, Blackwell T, Mernaugh RL, Robinson L, Fike C et al (2011) Oxidative injury is a common consequence of BMPR2 mutations. Pulm Circ 1:72–83
22. Liu D, Wu WH, Mao YM, Yuan P, Zhang R, Ju FL, Jing ZC (2012) BMPR2 mutations influence phenotype more obviously in male patients with pulmonary arterial hypertension. Circ Cardiovasc Genet 5:511–518
23. Long L, MacLean MR, Jeffery TK, Morecroft I, Yang X, Rudarakanchana N, Southwood M, James V, Trembath RC, Morrell NW (2006) Serotonin increases susceptibility to pulmonary hypertension in BMPR2-deficient mice. Circ Res 98:818–827
24. Long L, Ormiston ML, Yang X, Southwood M, Graf S, Machado RD, Mueller M, Kinzel B, Yung LM, Wilkinson JM et al (2015) Selective enhancement of endothelial BMPR-II with BMP9 reverses pulmonary arterial hypertension. Nat Med 21:777–785
25. Ma L, Chung WK (2014) The genetic basis of pulmonary arterial hypertension. Hum Genet 133:471–479
26. Machado RD, Pauciulo MW, Thomson JR, Lane KB, Morgan NV, Wheeler L, Phillips JA 3rd, Newman J, Williams D, Galie N et al (2001) BMPR2 haploinsufficiency as the inherited molecular mechanism for primary pulmonary hypertension. Am J Hum Genet 68:92–102
27. Machado RD, Rudarakanchana N, Atkinson C, Flanagan JA, Harrison R, Morrell NW, Trembath RC (2003) Functional interaction between BMPR-II and Tctex-1, a light chain of Dynein, is isoform-specific and disrupted by mutations underlying primary pulmonary hypertension. Hum Mol Genet 12:3277–3286
28. Machado RD, Aldred MA, James V, Harrison RE, Patel B, Schwalbe EC, Gruenig E, Janssen B, Koehler R, Seeger W et al (2006) Mutations of the TGF-beta type II receptor BMPR2 in pulmonary arterial hypertension. Hum Mutat 27:121–132
29. Majka S, Hagen M, Blackwell T, Harral J, Johnson JA, Gendron R, Paradis H, Crona D, Loyd JE, Nozik-Grayck E et al (2011) Physiologic and molecular consequences of endothelial Bmpr2 mutation. Respir Res 12:84
30. Mehari A, Valle O, Gillum RF (2014) Trends in pulmonary hypertension mortality and morbidity. Pulm Med 2014:105864
31. Nickel NP, Spiekerkoetter E, Gu M, Li CG, Li H, Kaschwich M, Diebold I, Hennigs JK, Kim KY, Miyagawa K et al (2015) Elafin reverses pulmonary hypertension via caveolin-1-dependent bone morphogenetic protein signaling. Am J Respir Crit Care Med 191:1273–1286
32. Peacock AJ, Murphy NF, McMurray JJ, Caballero L, Stewart S (2007) An epidemiological study of pulmonary arterial hypertension. Eur Respir J 30:104–109
33. Prewitt AR, Ghose S, Frump AL, Datta A, Austin ED, Kenworthy AK, de Caestecker MP (2015) Heterozygous null bone morphogenetic protein receptor type 2 mutations promote SRC kinase-dependent caveolar trafficking defects and endothelial dysfunction in pulmonary arterial hypertension. J Biol Chem 290:960–971
34. Ranchoux B, Antigny F, Rucker-Martin C, Hautefort A, Pechoux C, Bogaard HJ, Dorfmuller P, Remy S, Lecerf F, Plante S et al (2015) Endothelial-to-mesenchymal transition in pulmonary hypertension. Circulation 131:1006–1018
35. Reynolds AM, Xia W, Holmes MD, Hodge SJ, Danilov S, Curiel DT, Morrell NW, Reynolds PN (2007) Bone morphogenetic protein type 2 receptor gene therapy attenuates hypoxic pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 292:L1182–L1192
36. Reynolds AM, Holmes MD, Danilov SM, Reynolds PN (2012) Targeted gene delivery of BMPR2 attenuates pulmonary hypertension. Eur Respir J 39:329–343
37. Rhodes CJ, Im H, Cao A, Hennigs JK, Wang L, Sa S, Chen PI, Nickel NP, Miyagawa K, Hopper RK (2015) RNA seq reveals a novel pathway of endothelial dysfunction in pulmonary arterial hypertension. Am J Respir Crit Care Med 192:356–366
38. Sawada H, Saito T, Nickel NP, Alastalo TP, Glotzbach JP, Chan R, Haghighat L, Fuchs G, Januszyk M, Cao A et al (2014) Reduced BMPR2 expression induces GM-CSF translation and macrophage recruitment in humans and mice to exacerbate pulmonary hypertension. J Exp Med 211:263–280
39. Schermuly RT, Ghofrani HA, Wilkins MR, Grimminger F (2011) Mechanisms of disease: pulmonary arterial hypertension. Nat Rev Cardiol 8:443–455
40. Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A, Gomez Sanchez MA, Krishna Kumar R, Landzberg M, Machado RF et al (2013) Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 62:D34–D41
41. Sobolewski A, Rudarakanchana N, Upton PD, Yang J, Crilley TK, Trembath RC, Morrell NW (2008) Failure of bone morphogenetic protein receptor trafficking in pulmonary arterial hypertension: potential for rescue. Hum Mol Genet 17:3180–3190
42. Song Y, Jones JE, Beppu H, Keaney JF Jr, Loscalzo J, Zhang YY (2005) Increased susceptibility to pulmonary hypertension in heterozygous BMPR2-mutant mice. Circulation 112:553–562
43. Song Y, Coleman L, Shi J, Beppu H, Sato K, Walsh K, Loscalzo J, Zhang YY (2008) Inflammation, endothelial injury, and persistent pulmonary hypertension in heterozygous BMPR2-mutant mice. Am J Physiol Heart Circ Physiol 295:H677–H690
44. Soubrier F, Chung WK, Machado R, Grunig E, Aldred M, Geraci M, Loyd JE, Elliott CG, Trembath RC, Newman JH et al (2013) Genetics and genomics of pulmonary arterial hypertension. J Am Coll Cardiol 62:D13–D21
45. Spiekerkoetter E, Tian X, Cai J, Hopper RK, Sudheendra D, Li CG, El-Bizri N, Sawada H, Haghighat R, Chan R et al (2013) FK506 activates BMPR2, rescues endothelial dysfunction, and reverses pulmonary hypertension. J Clin Invest 123:3600–3613
46. Star GP, Giovinazzo M, Langleben D (2013) ALK2 and BMPR2 knockdown and endothelin-1 production by pulmonary microvascular endothelial cells. Microvasc Res 85:46–53
47. Wang Y, Zhang XH, Wang HL (2011) Involvement of BMPR2 in the protective effect of fluoxetine against monocrotaline-induced endothelial apoptosis in rats. Can J Physiol Pharmacol 89:345–354
48. Wang H, Ji R, Meng J, Cui Q, Zou W, Li L, Wang G, Sun L, Li Z, Huo L et al (2014) Functional changes in pulmonary arterial endothelial cells associated with BMPR2 mutations. PLoS ONE 9:e106703
49. West J, Niswender KD, Johnson JA, Pugh ME, Gleaves L, Fessel JP, Hemnes AR (2013) A potential role for insulin resistance in experimental pulmonary hypertension. Eur Respir J 41:861–871
50. West J, Austin E, Fessel JP, Loyd J, Hamid R (2014) Rescuing the BMPR2 signaling axis in pulmonary arterial hypertension. Drug Discov Today 19:1241–1245
51. Xiong J (2015) To be EndMT or not to be, that is the question in pulmonary hypertension. Protein Cell 6:547–550