Inflammatory mechanisms in the pathogenesis of pulmonary arterial hypertension

Comprehensive Physiology

Volumn 1, Issue 4, 2011, Pages 1929-1941

  Chami, Hala El ^a   Hassoun, Paul M ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AUTACOID; AUTOANTIBODY; SIGNAL PEPTIDE; TRANSCRIPTION FACTOR;

ANIMAL; ARTICLE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOLOGY; INFLAMMATION; METABOLISM; PULMONARY HYPERTENSION;

ANIMALS; AUTOANTIBODIES; HIV INFECTIONS; HUMANS; HYPERTENSION, PULMONARY; INFLAMMATION; INFLAMMATION MEDIATORS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; TRANSCRIPTION FACTORS;

HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 84862173741     PISSN: None     EISSN: 20404603     Source Type: Journal    
DOI: 10.1002/cphy.c100028     Document Type: Article

References (153)

1. Aaronson DS, Horvath CM. A road map for those who don't know JAK-STAT. Science 296(5573): 1653-1655, 2002.
2. Ali SA, Huang MB, Campbell PE, Roth WW, Campbell T, Khan M, Newman G, Villinger F, Powell MD, Bond VC. Genetic characterization of HIV type 1 Nef-induced vesicle secretion. AIDS Res Hum Retroviruses 26(2): 173-192, 2010.
3. Archer SL, Gomberg-Maitland M, Maitland ML, Rich S, Garcia JG, Weir EK. Mitochondrial metabolism, redox signaling, and fusion: A mitochondria-ROS-HIF-1alpha-Kv1.5 O2-sensing pathway at the intersection of pulmonary hypertension and cancer. Am J Physiol Heart Circ Physiol 294(2): H570-H578, 2008.
4. 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 105(14): 1672-1678, 2002.
5. Balabanian K, Foussat A, Dorfmuller P, Durand-Gasselin I, Capel F, Bouchet-Delbos L, Portier A, Marfaing-Koka A, Krzysiek R, Rimaniol AC, Simonneau G, Emilie D, Humbert M. CX(3)C chemokine fractalkine in pulmonary arterial hypertension. Am J Respir Crit Care Med 165(10): 1419-1425, 2002.
6. Balasubramaniam V, Le Cras TD, Ivy DD, Grover TR, Kinsella JP, Abman SH. Role of platelet-derived growth factor in vascular remodeling during pulmonary hypertension in the ovine fetus. Am J Physiol Lung Cell Mol Physiol 284(5): L826-L833, 2003.
7. Banasova A, Maxova H, Hampl V, Vizek M, Povysilova V, Novotna J, Vajnerova O, Hnilickova O, Herget J. Prevention of mast cell degranulation by disodium cromoglycate attenuates the development of hypoxic pulmonary hypertension in rats exposed to chronic hypoxia. Respiration 76(1): 102-107, 2008.
8. Banks MF, Gerasimovskaya EV, Tucker DA, Frid MG, Carpenter TC, Stenmark KR. Egr-1 antisense oligonucleotides inhibit hypoxiainduced proliferation of pulmonary artery adventitial fibroblasts. J Appl Physiol 98(2): 732-738, 2005.
9. Barkett M, Gilmore TD. Control of apoptosis by Rel/NF-kappaB transcription factors. Oncogene 18(49): 6910-6924, 1999.
10. Barst RJ, Rubin LJ, Long WA, McGoon MD, Rich S, Badesch DB, Groves BM, Tapson VF, Bourge RC, Brundage BH. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. The Primary Pulmonary Hypertension Study Group. N Engl J Med 334(5): 296-302, 1996.
11. Benekli M, Baer MR, Baumann H, Wetzler M. Signal transducer and activator of transcription proteins in leukemias. Blood 101(8): 2940-2954, 2003.
12. Bonnet S, Michelakis ED, Porter CJ, Andrade-Navarro MA, Thebaud B, Bonnet S, Haromy A, Harry G, Moudgil R, McMurtry MS, Weir EK, Archer SL. An abnormal mitochondrial-hypoxia inducible factor-1alpha-Kv channel pathway disrupts oxygen sensing and triggers pulmonary arterial hypertension in fawn hooded rats: Similarities to human pulmonary arterial hypertension. Circulation 113(22): 2630-2641, 2006.
13. Bonnet S, Rochefort G, Sutendra G, Archer SL, Haromy A, Webster L, Hashimoto K, Bonnet SN, Michelakis ED. The nuclear factor of activated T cells in pulmonary arterial hypertension can be therapeutically targeted. Proc Natl Acad Sci U S A 104(27): 11418-11423, 2007.
14. Brandstrom H, Bjorkman T, Ljunggren O. Regulation of osteoprotegerin secretion from primary cultures of human bone marrow stromal cells. Biochem Biophys Res Commun N Engl J Med 280(3): 831-835, 2001.
15. Budhiraja R, Tuder RM, Hassoun PM. Endothelial dysfunction in pulmonary hypertension. Circulation 109(2): 159-165, 2004.
16. Bushdid PB, Osinska H, Waclaw RR, Molkentin JD, Yutzey KE. NFATc3 and NFATc4 are required for cardiac development and mitochondrial function. Circ Res 92(12): 1305-1313, 2003.
17. Chaouat A, Savale L, Chouaid C, Tu L, Sztrymf B, CanuetM, Maitre B, Housset B, Brandt C, Le Corvoisier P, Weitzenblum E, Eddahibi S, Adnot S. Role for interleukin-6 in COPD-related pulmonary hypertension. Chest 136(3): 678-687, 2009.
18. Chizzolini C, Raschi E, Rezzonico R, Testoni C, Mallone R, Gabrielli A, Facchini A, Del Papa N, Borghi MO, Dayer JM, Meroni PL. Autoantibodies to fibroblasts induce a proadhesive and proinflammatory fibroblast phenotype in patients with systemic sclerosis. Arthritis Rheum 46(6): 1602-1613, 2002.
19. Christou H, Yoshida A, Arthur V, Morita T, Kourembanas S. Increased vascular endothelial growth factor production in the lungs of rats with hypoxia-induced pulmonary hypertension. Am J Respir Cell Mol Biol 18(6): 768-776., 1998.
20. Collins KL, Chen BK, Kalams SA, Walker BD, Baltimore D. HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes. Nature 391(6665): 397-401, 1998.
21. 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 155(2): 411-419, 1999.
22. Cox CP, Linden J, Said SI. VIP elevates platelet cyclic AMP (cAMP) levels and inhibits in vitro platelet activation induced by plateletactivating factor (PAF). Peptides 5(2): 325-328, 1984.
23. Crona D, Harral J, Adnot S, Eddahibi S, West J. Gene expression in lungs of mice lacking the 5-hydroxytryptamine transporter gene. BMC Pulm Med 9: 19, 2009.
24. D'Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, Fishman AP, Goldring RM, Groves BM, Kernis JT. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med 115(5): 343-349, 1991.
25. DempsieY, Morecroft I, WelshDJ, MacritchieNA, HeroldN, Loughlin L, Nilsen M, Peacock AJ, Harmar A, Bader M, Maclean MR. Converging evidence in support of the serotonin hypothesis of dexfenfluramineinduced pulmonary hypertension with novel transgenic mice. Circulation 117(22): 2928-2937, 2008.
26. Denk A, Goebeler M, Schmid S, Berberich I, Ritz O, Lindemann D, Ludwig S, Wirth T. Activation of NF-kappa B via the Ikappa B kinase complex is both essential and sufficient for proinflammatory gene expression in primary endothelial cells. J Biol Chem 276(30): 28451-28458, 2001.
27. Dorfmuller P, Humbert M, Perros F, Sanchez O, Simonneau G, Muller KM, Capron F. Fibrous remodeling of the pulmonary venous system in pulmonary arterial hypertension associated with connective tissue diseases. Hum Pathol 38(6): 893-902, 2007.
28. Dorfmuller P, Zarka V, Durand-Gasselin I, Monti G, Balabanian K, Garcia G, Capron F, Coulomb-Lhermine A, Marfaing-Koka A, Simonneau G, Emilie D, Humbert M. Chemokine RANTES in severe pulmonary arterial hypertension. Am J Respir Crit Care Med 165(4): 534-539, 2002.
29. Eddahibi S, Fabre V, Boni C, Martres MP, Raffestin B, Hamon M, Adnot S. Induction of serotonin transporter by hypoxia in pulmonary vascular smooth muscle cells. Relationship with the mitogenic action of serotonin. Circ Res 84(3): 329-336, 1999.
30. Eddahibi S, Hanoun N, Lanfumey L, Lesch KP, Raffestin B, HamonM, Adnot S. Attenuated hypoxic pulmonary hypertension in mice lacking the 5-hydroxytryptamine transporter gene. J Clin Invest 105(11): 1555-1562, 2000.
31. 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 108(8): 1141-1150, 2001.
32. Eddahibi S, Humbert M, Fadel E, Raffestin B, Darmon M, Capron F, Simonneau G, Dartevelle P, Hamon M, Adnot S. Hyperplasia of pulmonary artery smoothmuscle cells is causally related to overexpression of the serotonin transporter in primary pulmonary hypertension. Chest 121(3 Suppl): 97S-98S, 2002.
33. Eddahibi S, Humbert M, Sediame S, Chouaid C, Partovian C, Maitre B, Teiger E, Rideau D, Simonneau G, Sitbon O, Adnot S. Imbalance between platelet vascular endothelial growth factor and platelet-derived growth factor in pulmonary hypertension. Effect of prostacyclin therapy. Am J Respir Crit Care Med 162(4 Pt 1): 1493-1499, 2000
34. Ehrenreich H, Rieckmann P, Sinowatz F, Weih KA, Arthur LO, Goebel FD, Burd PR, Coligan JE, Clouse KA. Potent stimulation of monocytic endothelin-1 production by HIV-1 glycoprotein 120. J Immunol 150(10): 4601-4609, 1993.
35. Fanburg BL, Lee SL. A new role for an old molecule: Serotonin as a mitogen. Am J Physiol 272(5 Pt 1): L795-L806, 1997.
36. Fartoukh M, Emilie D, Le Gall C, Monti G, Simonneau G, Humbert M. Chemokine macrophage inflammatory protein-1alpha mRNA expression in lung biopsy specimens of primary pulmonary hypertension. Chest 114(1 Suppl): 50S-51S, 1998.
37. Friedman R, Mears JG, Barst RJ. Continuous infusion of prostacyclin normalizes plasma markers of endothelial cell injury and platelet aggregation in primary pulmonary hypertension. Circulation 96(9): 2782-2784, 1997.
38. Fritzler MJ, Hart DA, Wilson D, Garcia-De La Torre I, Salazar-Paramo M, Vazquez-Del Mercado M, Senecal JL, Loyau S, Angles-Cano E. Antibodies to fibrin bound tissue type plasminogen activator in systemic sclerosis. J Rheumatol 22(9): 1688-1693, 1995.
39. Fu M, Zhu X, Zhang J, Liang J, Lin Y, Zhao L, Ehrengruber MU, Chen YE. Egr-1 target genes in human endothelial cells identified by microarray analysis. Gene 315: 33-41, 2003.
40. Galie N, Brundage BH, Ghofrani HA, Oudiz RJ, Simonneau G, Safdar Z, Shapiro S, White RJ, Chan M, Beardsworth A, Frumkin L, Barst RJ. Tadalafil therapy for pulmonary arterial hypertension. Circulation 119(22): 2894-2903, 2009.
41. Gerasimovskaya EV, Ahmad S, White CW, Jones PL, Carpenter TC, Stenmark KR. Extracellular ATP is an autocrine/paracrine regulator of hypoxia-induced adventitial fibroblast growth. Signaling through extracellular signal-regulated kinase-1/2 and the Egr-1 transcription factor. J Biol Chem 277(47): 44638-44650, 2002.
42. Golembeski SM, West J, Tada Y, Fagan KA. Interleukin-6 causes mild pulmonary hypertension and augments hypoxia-induced pulmonary hypertension in mice. Chest 128(6 Suppl): 572S-573S, 2005.
43. Gordon JR, Burd PR, Galli SJ. Mast cells as a source of multifunctional cytokines. Immunol Today 11(12): 458-464, 1990.
44. Grigolo B, Mazzetti I, Meliconi R, Bazzi S, Scorza R, Candela M, Gabrielli A, Facchini A. Anti-topoisomerase II alpha autoantibodies in systemic sclerosis-association with pulmonary hypertension and HLAB35. Clin Exp Immunol 121(3): 539-543, 2000.
45. Guignabert C, Izikki M, Tu LI, Li Z, Zadigue P, Barlier-Mur AM, Hanoun N, Rodman D, Hamon M, Adnot S, Eddahibi S. Transgenic mice overexpressing the 5-hydroxytryptamine transporter gene in smooth muscle develop pulmonary hypertension. Circ Res 98(10): 1323-1330, 2006.
46. Guignabert C, Raffestin B, Benferhat R, Raoul W, Zadigue P, Rideau D, Hamon M, Adnot S, Eddahibi S. Serotonin transporter inhibition prevents and reverses monocrotaline-induced pulmonary hypertension in rats. Circulation 111(21): 2812-2819, 2005.
47. Gustafsson BI, Thommesen L, Stunes AK, Tommeras K, Westbroek I, Waldum HL, Slordahl K, Tamburstuen MV, Reseland JE, Syversen U. Serotonin and fluoxetine modulate bone cell function in vitro. J Cell Biochem 98(1): 139-151, 2006.
48. Hamidi SA, Prabhakar S, Said SI. Enhancement of pulmonary vascular remodelling and inflammatory genes with VIP gene deletion. Eur Respir J 31(1): 135-139, 2008.
49. Hassoun PM, Mouthon L, Barbera JA, Eddahibi S, Flores SC, Grimminger F, Jones PL, Maitland ML, Michelakis ED, Morrell NW, Newman JH, Rabinovitch M, Schermuly R, Stenmark KR, Voelkel NF, Yuan JX, Humbert M. Inflammation, growth factors, and pulmonary vascular remodeling. J Am Coll Cardiol 54(1 Suppl): S10-S19, 2009.
50. Henning RJ, Sawmiller DR. Vasoactive intestinal peptide: Cardiovascular effects. Cardiovasc Res 49(1): 27-37, 2001.
51. Herget J, Suggett AJ, Leach E, Barer GR. Resolution of pulmonary hypertension and other features induced by chronic hypoxia in rats during complete and intermittent normoxia. Thorax 33(4): 468-473, 1978.
52. Herve P, Humbert M, Sitbon O, Parent F, Nunes H, Legal C, Garcia G, Simonneau G. Pathobiology of pulmonary hypertension. The role of platelets and thrombosis. Clin Chest Med 22(3): 451-458, 2001.
53. Hodge DR, Hurt EM, Farrar WL. The role of IL-6 and STAT3 in inflammation and cancer. Eur J Cancer 41(16): 2502-2512, 2005.
54. Hofbauer LC, Dunstan CR, Spelsberg TC, Riggs BL, Khosla S. Osteoprotegerin production by human osteoblast lineage cells is stimulated by vitamin D, bone morphogenetic protein-2, and cytokines. Biochem Biophys Res Commun 250(3): 776-781, 1998.
55. Hu Y, Bock G, Wick G, Xu Q. Activation of PDGF receptor alpha in vascular smooth muscle cells by mechanical stress. FASEB J 12(12): 1135-1142, 1998.
56. Humbert M. Mediators involved in HIV-related pulmonary arterial hypertension. AIDS 22(Suppl 3): S41-S47, 2008.
57. HumbertM, MontiG, Brenot F, Sitbon O, Portier A, Grangeot-Keros L, Duroux P, Galanaud P, Simonneau G, Emilie D. Increased interleukin-1 and interleukin-6 serum concentrations in severe primary pulmonary hypertension. Am J Respir Crit Care Med 151(5): 1628-1631, 1995.
58. Humbert M, Monti G, Fartoukh M, Magnan A, Brenot F, Rain B, Capron F, Galanaud P, Duroux P, Simonneau G, Emilie D. Plateletderived growth factor expression in primary pulmonary hypertension: Comparison of HIV seropositive and HIV seronegative patients. Eur Respir J 11(3): 554-559, 1998.
59. Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med 351(14): 1425-1436, 2004.
60. Isern RA, Yaneva M, Weiner E, Parke A, Rothfield N, Dantzker D, Rich S, Arnett FC. Autoantibodies in patients with primary pulmonary hypertension: Association with anti-Ku. Am J Med 93(3): 307-312, 1992.
61. Janosi T, Petak F, Fontao F, Morel DR, Beghetti M, Habre W. Differential roles of endothelin-1 ETA and ETB receptors and vasoactive intestinal polypeptide in regulation of the airways and the pulmonary vasculature in isolated rat lung. Exp Physiol 93(11): 1210-1219, 2008.
62. Jones PL, Cowan KN, Rabinovitch M. Tenascin-C, proliferation and subendothelial fibronectin in progressive pulmonary vascular disease. Am J Pathol 150(4): 1349-1360, 1997.
63. Jones PL, Rabinovitch M. Tenascin-C is induced with progressive pulmonary vascular disease in rats and is functionally related to increased smooth muscle cell proliferation. Circ Res 79(6): 1131-1142, 1996.
64. Kawamura C, Kizaki M, Yamato K, Uchida H, Fukuchi Y, Hattori Y, Koseki T, Nishihara T, Ikeda Y. Bone morphogenetic protein-2 induces apoptosis in human myeloma cells with modulation of STAT3. Blood 96(6): 2005-2011, 2000.
65. Kawamura T, Ono K, Morimoto T, Akao M, Iwai-Kanai E, Wada H, Sowa N, Kita T, Hasegawa K. Endothelin-1-dependent nuclear factor of activated T lymphocyte signaling associates with transcriptional coactivator p300 in the activation of the B cell leukemia-2 promoter in cardiac myocytes. Circ Res 94(11): 1492-1499, 2004.
66. Kempe S, Kestler H, Lasar A, Wirth T. NF-kappaB controls the global pro-inflammatory response in endothelial cells: Evidence for the regulation of a pro-atherogenic program. Nucleic Acids Res 33(16): 5308-5319, 2005.
67. Kentera D, Susic D, Veljkovic V, Tucakovic G, Koko V. Pulmonary artery pressure in rats with hereditary platelet function defect. Respiration 54(2): 110-114, 1988.
68. Khachigian LM, Lindner V, Williams AJ. Collins T. Egr-1-induced endothelial gene expression: A common theme in vascular injury. Science 271(5254): 1427-1431, 1996.
69. Klein M, Schermuly RT, Ellinghaus P, Milting H, Riedl B, Nikolova S, Pullamsetti SS, Weissmann N, Dony E, Savai R, Ghofrani HA, Grimminger F, Busch AE, Schafer S. Combined tyrosine and serine/ threonine kinase inhibition by sorafenib prevents progression of experimental pulmonary hypertension andmyocardial remodeling. Circulation 118(20): 2081-2090, 2008.
70. Kontogiorgis C, Hadjipavlou-Litina D. Thromboxane synthase inhibitors and thromboxane A(2) receptor antagonists: A quantitative structure activity relationships (QSARs) analysis. Curr Med Chem 17(28): 3162-3214, 2010.
71. Kwapiszewska G, Wilhelm J, Wolff S, Laumanns I, Koenig IR, Ziegler A, Seeger W, Bohle RM, Weissmann N, Fink L. Expression profiling of laser-microdissected intrapulmonary arteries in hypoxia-induced pulmonary hypertension. Respir Res 6: 109, 2005.
72. Lawrie A, Waterman E, Southwood M, Evans D, Suntharalingam J, Francis S, Crossman D, Croucher P, Morrell N, Newman C. Evidence of a role for osteoprotegerin in the pathogenesis of pulmonary arterial hypertension. Am J Pathol 172(1): 256-264, 2008.
73. Lee SL, Wang WW, Finlay GA, Fanburg BL. Serotonin stimulates mitogen-activated protein kinase activity through the formation of superoxide anion. Am J Physiol 277(2 Pt 1): L282-L291, 1999.
74. Lee SL, Wang WW, Moore BJ, Fanburg BL. Dual effect of serotonin on growth of bovine pulmonary artery smooth muscle cells in culture. Circ Res 68(5): 1362-1368, 1991.
75. Leuchte HH, Baezner C, BaumgartnerRA, BevecD, Bacher G, Neurohr C, Behr J. Inhalation of vasoactive intestinal peptide in pulmonary hypertension. Eur Respir J 32(5): 1289-1294, 2008.
76. Li P, Oparil S, Sun JZ, Thompson JA, Chen YF. Fibroblast growth factor mediates hypoxia-induced endothelin-a receptor expression in lung artery smooth muscle cells. J Appl Physiol 95(2): 643-651; discussion 863, 2003.
77. Lundquist CA, TobiumeM, Zhou J, UnutmazD, Aiken C. Nef-mediated downregulation of CD4 enhances human immunodeficiency virus type 1 replication in primary T lymphocytes. J Virol 76(9): 4625-4633, 2002.
78. Macian F. NFAT proteins: Key regulators of T-cell development and function. Nat Rev Immunol 5(6): 472-484, 2005.
79. MacLean MR, Deuchar GA, Hicks MN, Morecroft I, Shen S, Sheward J, Colston J, Loughlin L, Nilsen M, Dempsie Y, Harmar A. Overexpression of the 5-hydroxytryptamine transporter gene: Effect on pulmonary hemodynamics and hypoxia-induced pulmonary hypertension. Circulation 109(17): 2150-2155, 2004.
80. MacLean MR, Herve P, Eddahibi S, Adnot S. 5-hydroxytryptamine and the pulmonary circulation: Receptors, transporters and relevance to pulmonary arterial hypertension. Br J Pharmacol 131(2): 161-168, 2000.
81. Marecki J, Cool C, Voelkel N, Luciw P, Flores S. Evidence for vascular remodeling in the lungs of macaques infected with simian immunodeficiency virus/HIV NEF recombinant virus. Chest 128(6 Suppl): 621S-622S, 2005.
82. Marecki JC, Cool CD, Parr JE, Beckey VE, Luciw PA, Tarantal AF, Carville A, Shannon RP, Cota-GomezA, Tuder RM, Voelkel NF, Flores SC. HIV-1 Nef is associated with complex pulmonary vascular lesions in SHIV-nef-infected macaques. Am J Respir Crit Care Med 174(4): 437-445, 2006.
83. Masri FA, Xu W, Comhair SA, Asosingh K, KooM, 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 293(3): L548-L554, 2007.
84. Maxova H, Vasilkova M, Novotna J, Vajnerova O, Banasova A, Vizek M, Herget J. Prevention of mast cell degranulation by disodium cromoglycate delayed the regression of hypoxic pulmonary hypertension in rats. Respiration 80(4): 335-339, 2010.
85. McMahon G. VEGF receptor signaling in tumor angiogenesis. Oncologist 5(Suppl 1): 3-10, 2000.
86. Merklinger SL, Jones PL, Martinez EC, Rabinovitch M. Epidermal growth factor receptor blockademediates smooth muscle cell apoptosis and improves survival in rats with pulmonary hypertension. Circulation 112(3): 423-431, 2005.
87. Mette SA, Palevsky HI, Pietra GG, Williams TM, Bruder E, Prestipino AJ, Patrick AM, Wirth JA. Primary pulmonary hypertension in association with human immunodeficiency virus infection. A possible viral etiology for some forms of hypertensive pulmonary arteriopathy. Am Rev Respir Dis 145(5): 1196-1200, 1992.
88. Meyer GE, Yu E, Siegal JA, Petteway JC, Blumenstein BA, Brawer MK. Serum basic fibroblast growth factor in men with and without prostate carcinoma. Cancer 76(11): 2304-2311, 1995.
89. Michelakis ED, McMurtryMS, Wu XC, Dyck JR, Moudgil R, Hopkins TA, Lopaschuk GD, Puttagunta L, Waite R, Archer SL. Dichloroacetate, a metabolic modulator, prevents and reverses chronic hypoxic pulmonary hypertension in rats: Role of increased expression and activity of voltage-gated potassium channels. Circulation 105(2): 244-250, 2002.
90. Montani D, Chaouat A. Diagnosis and classification of pulmonary hypertension. Presse Med 39(Suppl 1): 1S3-15, 2010.
91. Morrell NW. Pulmonary hypertension due to BMPR2 mutation: A new paradigm for tissue remodeling? Proc Am Thorac Soc 3(8): 680-686, 2006.
92. 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 104(7): 790-795, 2001.
93. Morse JH, Barst RJ, FotinoM, Zhang Y, Flaster E, Gharavi AE, Fritzler MJ, Dominguez M, Angles-Cano E. Primary pulmonary hypertension, tissue plasminogen activator antibodies, and HLA-DQ7. Respir Crit Care Med 155(1): 274-278, 1997.
94. Negi VS, Tripathy NK, Misra R, Nityanand S. Antiendothelial cell antibodies in scleroderma correlate with severe digital ischemia and pulmonary arterial hypertension. J Rheumatol 25(3): 462-466, 1998.
95. Newman JH, Fanburg BL, Archer SL, Badesch DB, Barst RJ, Garcia JG, Kao PN, Knowles JA, Loyd JE, McGoonMD, Morse JH, Nichols WC, Rabinovitch M, Rodman DM, Stevens T, Tuder RM, Voelkel NF, Gail DB, National Heart, Lung and Blood Institute/Office of Rare Diseases. Pulmonary arterial hypertension: Future directions: Report of a National Heart, Lung and Blood Institute/Office of Rare Diseases workshop. Circulation 109(24): 2947-2952, 2004.
96. Nicolls MR, Taraseviciene-Stewart L, Rai PR, Badesch DB, Voelkel NF. Autoimmunity and pulmonary hypertension: A perspective. Eur Respir J 26(6): 1110-1118, 2005.
97. Nishizuka Y, Sakakura T. Thymus and reproduction: Sex-linked dysgenesia of the gonad after neonatal thymectomy in mice. Science 166(906): 753-755, 1969.
98. Okano Y, Steen VD, Medsger TA, Jr. Autoantibody to U3 nucleolar ribonucleoprotein (fibrillarin) in patients with systemic sclerosis. Arthritis Rheum 35(1): 95-100, 1992.
99. Okawa-TakatsujiM, Aotsuka S, FujinamiM, Uwatoko S, Kinoshita M, Sumiya M. Up-regulation of intercellular adhesion molecule-1 (ICAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1) and class II MHC molecules on pulmonary artery endothelial cells by antibodies against U1-ribonucleoprotein. Clin Exp Immunol 116(1): 174-180, 1999.
100. Olivetta E, Percario Z, Fiorucci G, Mattia G, Schiavoni I, Dennis C, Jager J, Harris M, Romeo G, Affabris E, Federico M. HIV-1 Nef induces the release of inflammatory factors from human monocyte/ macrophages: Involvement of Nef endocytotic signals and NFkappa B activation. J Immunol 170(4): 1716-1727, 2003.
101. Pahl HL. Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene 18(49): 6853-6866, 1999.
102. Peacock AJ, Murphy NF, McMurray JJ, Caballero L, Stewart S. An epidemiological study of pulmonary arterial hypertension. Eur Respir J 30(1): 104-109, 2007.
103. Penhale WJ, Farmer A, McKenna RP, Irvine WJ. Spontaneous thyroiditis in thymectomized and irradiatedWistar rats. Clin Exp Immunol 15(2): 225-236, 1973.
104. Penhale WJ, Irvine WJ, Inglis JR, Farmer A. Thyroiditis in T celldepleted rats: Suppression of the autoallergic response by reconstitution with normal lymphoid cells. Clin Exp Immunol 25(1): 6-16, 1976.
105. Pepper MS. Transforming growth factor-beta: Vasculogenesis, angiogenesis, and vessel wall integrity. Cytokine Growth Factor Rev 8(1): 21-43, 1997.
106. Perros F, Dorfmuller P, Souza R, Durand-Gasselin I, Godot V, Capel F, Adnot S, Eddahibi S, Mazmanian M, Fadel E, Herve P, Simonneau G, Emilie D, Humbert M. Fractalkine-induced smooth muscle cell proliferation in pulmonary hypertension. Euro Respir J 29(5): 937-943, 2007.
107. Perros F, Montani D, Dorfmuller P, Durand-Gasselin I, Tcherakian C, Le Pavec J, Mazmanian M, Fadel E, Mussot S, Mercier O, Herve P, Emilie D, Eddahibi S, Simonneau G, Souza R, Humbert M. Platelet derived growth factor expression and function in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 178(1): 81-88, 2008.
108. Petkov V, Mosgoeller W, Ziesche R, Raderer M, Stiebellehner L, Vonbank K, Funk GC, Hamilton G, Novotny C, Burian B, Block LH. Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension. J Clin Invest 111(9): 1339-1346, 2003.
109. Prasse A, Zissel G, Lutzen N, Schupp J, Schmiedlin R, Gonzalez-Rey E, Rensing-Ehl A, Bacher G, Cavalli V, Bevec D, Delgado M, Muller-Quernheim J. Inhaled vasoactive intestinal peptide exerts immunoregulatory effects in sarcoidosis. Am J Respir Crit Care Med 182(4): 540-548 2010.
110. Quinn TP, Schlueter M, Soifer SJ, Gutierrez JA. Cyclic mechanical stretch induces VEGF and FGF-2 expression in pulmonary vascular smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 282(5): L897-L903, 2002.
111. Rich S, Dantzker DR, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, Fishman AP, Goldring RM, Groves BM, Koerner SK. Primary pulmonary hypertension. A national prospective study. Ann InternMed 107(2): 216-223, 1987.
112. Rich S, McLaughlin VV. Endothelin receptor blockers in cardiovascular disease. Circulation 108(18): 2184-2190, 2003.
113. Rossow CF, Minami E, Chase EG, Murry CE, Santana LF. NFATc3-induced reductions in voltage-gated K+ currents after myocardial infarction. Circ Res 94(10): 1340-1350, 2004.
114. Roth M, Nauck M, Yousefi S, Tamm M, Blaser K, Perruchoud AP, Simon HU. Platelet-activating factor exerts mitogenic activity and stimulates expression of interleukin 6 and interleukin 8 in human lung fibroblasts via binding to its functional receptor. J ExpMed J Exp Med 184(1): 191-201, 1996.
115. Said SI, Hamidi SA, Dickman KG, Szema AM, Lyubsky S, Lin RZ, Jiang YP, Chen JJ, Waschek JA, Kort S. Moderate pulmonary arterial hypertension in male mice lacking the vasoactive intestinal peptide gene. Circulation 115(10): 1260-1268, 2007.
116. Sakaguchi S, Takahashi T, Nishizuka Y. Study on cellular events in postthymectomy autoimmune oophoritis in mice. I. Requirement of Lyt-1 effector cells for oocytes damage after adoptive transfer. J Exp Med 156(6): 1565-1576, 1982.
117. Sakamaki F, Kyotani S, Nagaya N, Sato N, Oya H, Satoh T, Nakanishi N. Increased plasma P-selectin and decreased thrombomodulin in pulmonary arterial hypertension were improved by continuous prostacyclin therapy. Circulation 102(22): 2720-2725, 2000.
118. Sakao S, Taraseviciene-Stewart L, Cool CD, Tada Y, Kasahara Y, Kurosu K, Tanabe N, Takiguchi Y, Tatsumi K, Kuriyama T, Voelkel NF. VEGF-R blockade causes endothelial cell apoptosis, expansion of surviving CD34+ precursor cells and transdifferentiation to smooth muscle-like and neuronal-like cells. FASEB J 21(13): 3640-3652, 2007.
119. Sanchez O, Marcos E, Perros F, Fadel E, Tu L, Humbert M, Dartevelle P, Simonneau G, Adnot S, Eddahibi S. Role of endothelium-derived CC chemokine ligand 2 in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 176(10): 1041-1047, 2007.
120. Savale L, Tu L, Rideau D, Izziki M, Maitre B, Adnot S, Eddahibi S. Impact of interleukin-6 on hypoxia-induced pulmonary hypertension and lung inflammation in mice. Respir Res 10: 6, 2009.
121. Schermuly RT, Dony E, Ghofrani HA, Pullamsetti S, Savai R, Roth M, Sydykov A, Lai YJ, Weissmann N, SeegerW, Grimminger F. Reversal of experimental pulmonary hypertension by PDGF inhibition. J Clin Invest 115(10): 2811-2821, 2005.
122. Selimovic N, Bergh CH, Andersson B, Sakiniene E, Carlsten H, Rundqvist B. Growth factors and interleukin-6 across the lung circulation in pulmonary hypertension. Eur Respir J 34(3): 662-668, 2009.
123. Semenza GL. Oxygen-regulated transcription factors and their role in pulmonary disease. Respir Res 1(3): 159-162, 2000.
124. Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, ShimamotoG, DeRoseM, Elliott R, Colombero A, Tan HL, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes TM, Hill D, Pattison W, Campbell P, Sander S, Van G, Tarpley J, Derby P, Lee R, Boyle WJ. Osteoprotegerin: A novel secreted protein involved in the regulation of bone density. Cell 89(2): 309-319, 1997.
125. Simonneau G, Robbins IM, Beghetti M, Channick RN, Delcroix M, Denton CP, Elliott CG, Gaine SP, Gladwin MT, Jing ZC, Krowka MJ, Langleben D, Nakanishi N, Souza R. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 54(1 Suppl): S43-S54, 2009.
126. SteinerMK, Syrkina OL, KolliputiN, Mark EJ, Hales CA, WaxmanAB. Interleukin-6 overexpression induces pulmonary hypertension. Circ Res 104(2): 236-244, 28p following 244, 2009.
127. Swann SA, Williams M, Story CM, Bobbitt KR, Fleis R, Collins KL. HIV-1 Nef blocks transport ofMHC class I molecules to the cell surface via a PI 3-kinase-dependent pathway. Virology 282(2): 267-277, 2001.
128. Takahashi K, Nakanishi S, Imamura S. Direct effects of cutaneous neuropeptides on adenylyl cyclase activity and proliferation in a keratinocyte cell line: Stimulation of cyclic AMP formation by CGRP and VIP/PHM, and inhibition by NPY throughGprotein-coupled receptors. J Invest Dermatol 101(5): 646-651, 1993.
129. Tamby MC, Chanseaud Y, Humbert M, Fermanian J, Guilpain P, Garcia-de-la-Pena-Lefebvre P, Brunet S, Servettaz A, Weill B, Simonneau G, Guillevin L, Boissier MC, Mouthon L. Anti-endothelial cell antibodies in idiopathic and systemic sclerosis associated pulmonary arterial hypertension. Thorax 60(9): 765-772, 2005.
130. Tamby MC, Humbert M, Guilpain P, Servettaz A, Dupin N, Christner JJ, Simonneau G, Fermanian J, Weill B, Guillevin L, Mouthon L. Antibodies to fibroblasts in idiopathic and scleroderma-associated pulmonary hypertension. Eur Respir J 28(4): 799-807, 2006.
131. Taraseviciene-Stewart L, Scerbavicius R, Choe KH, Cool C, Wood K, Tuder RM, Burns N, Kasper M, Voelkel NF. Simvastatin causes endothelial cell apoptosis and attenuates severe pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 291(4): L668-L676, 2006.
132. Ten Dijke P, Goumans MJ, Itoh F, Itoh S. Regulation of cell proliferation by Smad proteins. J Cell Physiol 191(1): 1-16, 2002.
133. Terrier B, TambyMC, Camoin L, Guilpain P, Broussard C, Bussone G, Yaici A, Hotellier F, Simonneau G, Guillevin L, Humbert M, Mouthon L. Identification of target antigens of antifibroblast antibodies in pulmonary arterial hypertension. Am J Res Crit Care Med 177(10): 1128-1134, 2008.
134. Tozzi CA, Thakker-Varia S, Yu SY, Bannett RF, Peng BW, Poiani GJ, Wilson FJ, Riley DJ. Mast cell collagenase correlates with regression of pulmonary vascular remodeling in the rat. Am J Respir Cell Mol Biol 18(4): 497-510, 1998.
135. Trembath RC, Thomson JR, Machado RD, Morgan NV, Atkinson C, Winship I, Simonneau G, Galie N, Loyd JE, Humbert M, NicholsWC, Morrell NW, Berg J, Manes A, McGaughran J, Pauciulo M, Wheeler L. Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia. N Engl J Med 345(5): 325-334, 2001.
136. Trumpp-Kallmeyer S, Hoflack J, Bruinvels A, Hibert M. Modeling of G-protein-coupled receptors: Application to dopamine, adrenaline, serotonin, acetylcholine, and mammalian opsin receptors. J Med Chem 35(19): 3448-3462, 1992.
137. Tsubata T, Wu J, Honjo T. B-cell apoptosis induced by antigen receptor crosslinking is blocked by a T-cell signal through CD40. Nature 364(6438): 645-648, 1993.
138. Tuder RM, Chacon M, Alger L, Wang J, Taraseviciene-Stewart L, Kasahara Y, Cool CD, Bishop AE, Geraci M, Semenza GL, Yacoub M, Polak JM, Voelkel NF. Expression of angiogenesis-related molecules in plexiform lesions in severe pulmonary hypertension: Evidence for a process of disordered angiogenesis. J Pathol 195(3): 367-374., 2001.
139. Tuder RM, Flook BE, Voelkel NF. Increased gene expression forVEGF and the VEGF receptors KDR/Flk and Flt in lungs exposed to acute or to chronic hypoxia. Modulation of gene expression by nitric oxide. J Clin Invest 95(4): 1798-1807, 1995.
140. Tuder RM, Groves B, Badesch DB, Voelkel NF. Exuberant endothelial cell growth and elements of inflammation are present in plexiform lesions of pulmonary hypertension. Am J Pathol 144(2): 275-285., 1994.
141. Ulrich S, Nicolls MR, Taraseviciene L, Speich R, Voelkel N. Increased regulatory and decreased CD8+ cytotoxic T cells in the blood of patients with idiopathic pulmonary arterial hypertension. Respiration 75(3): 272-280, 2008.
142. Voelkel NF, Cool C, Lee SD, Wright L, GeraciMW, TuderRM. Primary pulmonary hypertension between inflammation and cancer. Chest 114(3 Suppl): 225S-230S, 1998.
143. Vuckovic A, Rondelet B, Brion JP, Naeije R. Expression of vasoactive intestinal peptide and related receptors in overcirculation-induced pulmonary hypertension in piglets. Pediatr Res 66(4): 395-399, 2009.
144. Wang GS, Qian GS, Bai L, Chen Y, Wu GM, Zhou DS, Qian P. Enhanced expression of signal transducers and activators of transcription in lung tissue of hypoxic pulmonary hypertension ratmodels. Zhonghua Nei Ke Za Zhi 42(11): 768-772, 2003.
145. Wedgwood S, Devol JM, Grobe A, Benavidez E, Azakie A, Fineman JR, Black SM. Fibroblast growth factor-2 expression is altered in lambs with increased pulmonary blood flow and pulmonary hypertension. Pediatr Res 61(1): 32-36, 2007.
146. Wells A. EGF receptor. Int J Biochem Cell Biol 31(6): 637-643, 1999.
147. Xu W, Comhair SA, Zheng S, Chu SC, Marks-Konczalik J, Moss J, Haque SJ, Erzurum SC. STAT-1 and c-Fos interaction in nitric oxide synthase-2 gene activation. Am J Physiol Lung Cell Mol Physiol 285(1): L137-L148, 2003.
148. Xu W, Kaneko FT, Zheng S, Comhair SA, Janocha AJ, Goggans T, Thunnissen FB, Farver C, Hazen SL, Jennings C, Dweik RA, Arroliga AC, Erzurum SC. Increased arginase II and decreased NO synthesis in endothelial cells of patients with pulmonary arterial hypertension. FASEB J 18(14): 1746-1748, 2004.
149. Yawata H, Yasukawa K, Natsuka S, Murakami M, Yamasaki K, Hibi M, Taga T, Kishimoto T. Structure-function analysis of human IL-6 receptor: Dissociation of amino acid residues required for IL-6-binding and for IL-6 signal transduction through gp130. EMBO J 12(4): 1705-1712, 1993.
150. Yayon A, Klagsbrun M, Esko JD, Leder P, Ornitz DM. Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor. Cell 64(4): 841-848, 1991.
151. Yeager ME, Halley GR, Golpon HA, Voelkel NF, Tuder RM. Microsatellite instability of endothelial cell growth and apoptosis genes within plexiform lesions in primary pulmonary hypertension. Circ Res 88(1): E2-E11, 2001.
152. Yoshio T, Masuyama J, Mimori A, Takeda A, Minota S, Kano S. Endothelin-1 release from cultured endothelial cells induced by sera from patients with systemic lupus erythematosus. AnnRheum Dis 54(5): 361-365, 1995.
153. Zittermann SI, IssekutzAC. Basic fibroblast growth factor (bFGF, FGF-2) potentiates leukocyte recruitment to inflammation by enhancing endothelial adhesion molecule expression. Am J Pathol 168 (3): 835-846, 2006.