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Translational Vascular Medicine pp 213–229Cite as

Inflammation in Pulmonary Arterial Hypertension

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Abstract

The pathophysiology of PAH is not fully elucidated and no curative treatment is yet available. However, the presence of inflammatory cells and the intense release of inflammatory mediators in pulmonary PAH lesions, associated with the high level of pro-inflammatory cytokines and of autoantibodies targeting vascular components in the sera of patients, raise the question of the involvement of inflammation and autoimmunity in the initiation, the perpetuation, and/or the worsening of the ­disease. This review covers PAH immunopathological aspects with a special emphasis on the role of inflammation on the pulmonary vascular remodeling, the potential immunopathological mechanisms of PAH, the relevance of inflammatory mediators as prognostic and predictive markers in PAH, and on the immunomodulatory properties of current PAH therapies.

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References

  1. Galie N, Hoeper MM, Humbert M, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2009;34(6):1219–63.

    PubMed  CAS  Google Scholar 

  2. Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004;351(14):1425–36.

    PubMed  CAS  Google Scholar 

  3. Simonneau G, Robbins IM, Beghetti M, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2009;54(1 Suppl):S43–54.

    PubMed  Google Scholar 

  4. Girerd B, Montani D, Coulet F, et al. Clinical outcomes of pulmonary arterial hypertension in patients carrying an ACVRL1 (ALK1) mutation. Am J Respir Crit Care Med. 2010;181(8):851–61.

    PubMed  CAS  Google Scholar 

  5. Schermuly RT, Dony E, Ghofrani HA, et al. Reversal of experimental pulmonary hypertension by PDGF inhibition. J Clin Invest. 2005;115(10):2811–21.

    PubMed  CAS  Google Scholar 

  6. Klein M, Schermuly RT, Ellinghaus P, et al. Combined tyrosine and serine/threonine kinase inhibition by sorafenib prevents progression of experimental pulmonary hypertension and myocardial remodeling. Circulation. 2008;118(20):2081–90.

    PubMed  CAS  Google Scholar 

  7. Perros F, Montani D, Dorfmuller P, et al. Platelet-derived growth factor expression and function in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med. 2008;178(1):81–8.

    PubMed  CAS  Google Scholar 

  8. Souza R, Sitbon O, Parent F, Simonneau G, Humbert M. Long term imatinib treatment in pulmonary arterial hypertension. Thorax. 2006;61(8):736.

    PubMed  CAS  Google Scholar 

  9. Chen MH, Kerkela R, Force T. Mechanisms of cardiac dysfunction associated with tyrosine kinase inhibitor cancer therapeutics. Circulation. 2008;118(1):84–95.

    PubMed  Google Scholar 

  10. Kerkela R, Grazette L, Yacobi R, et al. Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat Med. 2006;12(8):908–16.

    PubMed  Google Scholar 

  11. Humbert M, Monti G, Brenot F, et al. Increased interleukin-1 and interleukin-6 serum concentrations in severe primary pulmonary hypertension. Am J Respir Crit Care Med. 1995;151(5):1628–31.

    PubMed  CAS  Google Scholar 

  12. Balabanian K, Foussat A, Dorfmuller P, et al. CX(3)C chemokine fractalkine in pulmonary arterial hypertension. Am J Respir Crit Care Med. 2002;165(10):1419–25.

    PubMed  Google Scholar 

  13. Sanchez O, Marcos E, Perros F, et al. Role of endothelium-derived CC chemokine ligand 2 in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med. 2007;176(10):1041–7.

    PubMed  CAS  Google Scholar 

  14. Dorfmuller P, Perros F, Balabanian K, Humbert M. Inflammation in pulmonary arterial hypertension. Eur Respir J. 2003;22(2):358–63.

    PubMed  CAS  Google Scholar 

  15. Tamby MC, Chanseaud Y, Humbert M, et al. Anti-endothelial cell antibodies in idiopathic and systemic sclerosis associated pulmonary arterial hypertension. Thorax. 2005;60(9):765–72.

    PubMed  CAS  Google Scholar 

  16. Terrier B, Tamby MC, Camoin L, et al. Identification of target antigens of antifibroblast antibo­dies in pulmonary arterial hypertension. Am J Respir Crit Care Med. 2008;177(10):1128–34.

    PubMed  CAS  Google Scholar 

  17. Price LC, Montani D, Tcherakian C, et al. Dexamethasone reverses monocrotaline-induced pulmonary arterial hypertension in rats. Eur Respir J. 2011;37(4):813–22.

    PubMed  CAS  Google Scholar 

  18. Voelkel NF, Tuder RM, Bridges J, Arend WP. Interleukin-1 receptor antagonist treatment reduces pulmonary hypertension generated in rats by monocrotaline. Am J Respir Cell Mol Biol. 1994;11(6):664–75.

    PubMed  CAS  Google Scholar 

  19. Ikeda Y, Yonemitsu Y, Kataoka C, et al. Anti-monocyte chemoattractant protein-1 gene therapy attenuates pulmonary hypertension in rats. Am J Physiol Heart Circ Physiol. 2002;283(5):H2021–8.

    PubMed  CAS  Google Scholar 

  20. Jouve P, Humbert M, Chauveheid MP, Jais X, Papo T. POEMS syndrome-related pulmonary hypertension is steroid-responsive. Respir Med. 2007;101(2):353–5.

    PubMed  Google Scholar 

  21. Jais X, Launay D, Yaici A, et al. Immunosuppressive therapy in lupus- and mixed connective tissue disease-associated pulmonary arterial hypertension: a retrospective analysis of twenty-three cases. Arthritis Rheum. 2008;58(2):521–31.

    PubMed  Google Scholar 

  22. Heath D, Edwards JE. The pathology of hypertensive pulmonary vascular disease; a description of six grades of structural changes in the pulmonary arteries with special reference to congenital cardiac septal defects. Circulation. 1958;18(4 Part 1):533–47.

    PubMed  CAS  Google Scholar 

  23. Perros F, Dorfmuller P, Souza R, et al. Dendritic cell recruitment in lesions of human and experimental pulmonary hypertension. Eur Respir J. 2007;29(3):462–8.

    PubMed  CAS  Google Scholar 

  24. Wilson DW, Segall HJ, Pan LC, Dunston SK. Progressive inflammatory and structural changes in the pulmonary vasculature of monocrotaline-treated rats. Microvasc Res. 1989;38(1):57–80.

    PubMed  CAS  Google Scholar 

  25. Stenmark KR, Meyrick B, Galie N, Mooi WJ, McMurtry IF. Animal models of pulmonary arterial hypertension: the hope for etiological discovery and pharmacological cure. Am J Physiol Lung Cell Mol Physiol. 2009;297(6):L1013–32.

    PubMed  CAS  Google Scholar 

  26. Steiner MK, Syrkina OL, Kolliputi N, Mark EJ, Hales CA, Waxman AB. Interleukin-6 overexpression induces pulmonary hypertension. Circ Res. 2009;104(2):236–44, 28p following 44.

    PubMed  CAS  Google Scholar 

  27. Hamidi SA, Prabhakar S, Said SI. Enhancement of pulmonary vascular remodelling and inflammatory genes with VIP gene deletion. Eur Respir J. 2008;31(1):135–9.

    PubMed  CAS  Google Scholar 

  28. Song Y, Coleman L, Shi J, et al. Inflammation, endothelial injury, and persistent pulmonary hypertension in heterozygous BMPR2-mutant mice. Am J Physiol Heart Circ Physiol. 2008;295(2):H677–90.

    PubMed  CAS  Google Scholar 

  29. Daley E, Emson C, Guignabert C, et al. Pulmonary arterial remodeling induced by a Th2 immune response. J Exp Med. 2008;205(2):361–72.

    PubMed  CAS  Google Scholar 

  30. Medoff BD, Okamoto Y, Leyton P, et al. Adiponectin deficiency increases allergic airway inflammation and pulmonary vascular remodeling. Am J Respir Cell Mol Biol. 2009;41(4):397–406.

    PubMed  CAS  Google Scholar 

  31. Sehgal PB, Mukhopadhyay S, Patel K, et al. Golgi dysfunction is a common feature in idiopathic human pulmonary hypertension and vascular lesions in SHIV-nef-infected macaques. Am J Physiol Lung Cell Mol Physiol. 2009;297(4):L729–37.

    PubMed  CAS  Google Scholar 

  32. Crosby A, Jones FM, Southwood M, et al. Pulmonary vascular remodeling correlates with lung eggs and cytokines in murine schistosomiasis. Am J Respir Crit Care Med. 2010;181(3):279–88.

    PubMed  CAS  Google Scholar 

  33. Perros F, Dorfmuller P, Souza R, et al. Fractalkine-induced smooth muscle cell proliferation in pulmonary hypertension. Eur Respir J. 2007;29(5):937–43.

    PubMed  CAS  Google Scholar 

  34. Savale L, Tu L, Rideau D, et al. Impact of interleukin-6 on hypoxia-induced pulmonary hypertension and lung inflammation in mice. Respir Res. 2009;10:6.

    PubMed  Google Scholar 

  35. Swain SD, Han S, Harmsen A, Shampeny K, Harmsen AG. Pulmonary hypertension can be a sequela of prior Pneumocystis pneumonia. Am J Pathol. 2007;171(3):790–9.

    PubMed  CAS  Google Scholar 

  36. Hagen M, Fagan K, Steudel W, et al. Interaction of interleukin-6 and the BMP pathway in pulmonary smooth muscle. Am J Physiol Lung Cell Mol Physiol. 2007;292(6):L1473–9.

    PubMed  CAS  Google Scholar 

  37. Sakaguchi S. Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol. 2004;22:531–62.

    PubMed  CAS  Google Scholar 

  38. Wing K, Sakaguchi S. Regulatory T cells exert checks and balances on self tolerance and autoimmunity. Nat Immunol. 2010;11(1):7–13.

    PubMed  CAS  Google Scholar 

  39. Baecher-Allan C, Hafler DA. Suppressor T cells in human diseases. J Exp Med. 2004;200(3):273–6.

    PubMed  CAS  Google Scholar 

  40. Crispin JC, Martinez A, Alcocer-Varela J. Quantification of regulatory T cells in patients with systemic lupus erythematosus. J Autoimmun. 2003;21(3):273–6.

    PubMed  Google Scholar 

  41. de Kleer IM, Wedderburn LR, Taams LS, et al. CD4  +  CD25 bright regulatory T cells actively regulate inflammation in the joints of patients with the remitting form of juvenile idiopathic arthritis. J Immunol. 2004;172(10):6435–43.

    PubMed  Google Scholar 

  42. Kriegel MA, Lohmann T, Gabler C, Blank N, Kalden JR, Lorenz HM. Defective suppressor function of human CD4+ CD25+ regulatory T cells in autoimmune polyglandular syndrome type II. J Exp Med. 2004;199(9):1285–91.

    PubMed  CAS  Google Scholar 

  43. Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA. Loss of functional suppression by CD4  +  CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med. 2004;199(7):971–9.

    PubMed  CAS  Google Scholar 

  44. Matarese G, Carrieri PB, La Cava A, et al. Leptin increase in multiple sclerosis associates with reduced number of CD4(+)CD25+ regulatory T cells. Proc Natl Acad Sci USA. 2005;102(14):5150–5.

    PubMed  CAS  Google Scholar 

  45. Nicolls MR, Taraseviciene-Stewart L, Rai PR, Badesch DB, Voelkel NF. Autoimmunity and pulmonary hypertension: a perspective. Eur Respir J. 2005;26(6):1110–8.

    PubMed  CAS  Google Scholar 

  46. 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. 2008;75(3):272–80.

    PubMed  CAS  Google Scholar 

  47. Austin ED, Rock MT, Mosse CA, et al. T lymphocyte subset abnormalities in the blood and lung in pulmonary arterial hypertension. Respir Med. 2010;104(3):454–62.

    PubMed  CAS  Google Scholar 

  48. Perros F, Cohen-Kaminsky S, Humbert M. Understanding the role of CD4  +  CD25 (high) (so-called regulatory) T cells in idiopathic pulmonary arterial hypertension. Respiration. 2008;75(3):253–6.

    PubMed  Google Scholar 

  49. Hachulla E, Gressin V, Guillevin L, et al. Early detection of pulmonary arterial hypertension in systemic sclerosis: a French nationwide prospective multicenter study. Arthritis Rheum. 2005;52(12):3792–800.

    PubMed  Google Scholar 

  50. Haroon N, Nisha RS, Chandran V, Bharadwaj A. Pulmonary hypertension not a major feature of early mixed connective tissue disease: a prospective clinicoserological study. J Postgrad Med. 2005;51(2):104–7. discussion 7–8.

    PubMed  Google Scholar 

  51. Fois E, Le Guern V, Dupuy A, Humbert M, Mouthon L, Guillevin L. Noninvasive assessment of systolic pulmonary artery pressure in systemic lupus erythematosus: retrospective analysis of 93 patients. Clin Exp Rheumatol. 2010;28(6):836–41.

    PubMed  CAS  Google Scholar 

  52. Launay D, Hachulla E, Hatron PY, Jais X, Simonneau G, Humbert M. Pulmonary arterial hypertension: a rare complication of primary Sjogren syndrome: report of 9 new cases and review of the literature. Medicine (Baltimore). 2007;86(5):299–315.

    Google Scholar 

  53. Nunes H, Humbert M, Capron F, et al. Pulmonary hypertension associated with sarcoidosis: mechanisms, haemodynamics and prognosis. Thorax. 2006;61(1):68–74.

    PubMed  CAS  Google Scholar 

  54. Minai OA. Pulmonary hypertension in polymyositis-dermatomyositis: clinical and hemodynamic characteristics and response to vasoactive therapy. Lupus. 2009;18(11):1006–10.

    PubMed  CAS  Google Scholar 

  55. Chu JW, Kao PN, Faul JL, Doyle RL. High prevalence of autoimmune thyroid disease in pulmonary arterial hypertension. Chest. 2002;122(5):1668–73.

    PubMed  Google Scholar 

  56. Launay D, Souza R, Guillevin L, et al. Pulmonary arterial hypertension in ANCA-associated vasculitis. Sarcoidosis Vasc Diffuse Lung Dis. 2006;23(3):223–8.

    PubMed  Google Scholar 

  57. Garcia-Hernandez FJ, Ocana-Medina C, Gonzalez-Leon R, Garrido-Rasco R, Sanchez-Roman J. Autoimmune polyglandular syndrome and pulmonary arterial hypertension. Eur Respir J. 2006;27(3):657–8.

    PubMed  CAS  Google Scholar 

  58. Sitbon O, Lascoux-Combe C, Delfraissy JF, et al. Prevalence of HIV-related pulmonary arterial hypertension in the current antiretroviral therapy era. Am J Respir Crit Care Med. 2008;177(1):108–13.

    PubMed  Google Scholar 

  59. Lapa M, Dias B, Jardim C, et al. Cardiopulmonary manifestations of hepatosplenic schistosomiasis. Circulation. 2009;119(11):1518–23.

    PubMed  Google Scholar 

  60. Montani D, Achouh L, Marcelin AG, et al. Reversibility of pulmonary arterial hypertension in HIV/HHV8-associated Castleman’s disease. Eur Respir J. 2005;26(5):969–72.

    PubMed  CAS  Google Scholar 

  61. 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. 1994;144(2):275–85.

    PubMed  CAS  Google Scholar 

  62. Karmochkine M, Cacoub P, Dorent R, et al. High prevalence of antiphospholipid antibodies in precapillary pulmonary hypertension. J Rheumatol. 1996;23(2):286–90.

    PubMed  CAS  Google Scholar 

  63. Riboldi P, Gerosa M, Raschi E, Testoni C, Meroni PL. Endothelium as a target for antiphospholipid antibodies. Immunobiology. 2003;207(1):29–36.

    PubMed  CAS  Google Scholar 

  64. Mouthon L, Guillevin L, Humbert M. Pulmonary arterial hypertension: an autoimmune disease? Eur Respir J. 2005;26(6):986–8.

    PubMed  CAS  Google Scholar 

  65. Arends SJ, Damoiseaux J, Duijvestijn A, et al. Prevalence of anti-endothelial cell antibodies in idiopathic pulmonary arterial hypertension. Eur Respir J. 2010;35(4):923–5.

    PubMed  CAS  Google Scholar 

  66. Taraseviciene-Stewart L, Kasahara Y, Alger L, et al. 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(2):427–38.

    PubMed  CAS  Google Scholar 

  67. Renaudineau Y, Dugue C, Dueymes M, Youinou P. Antiendothelial cell antibodies in systemic lupus erythematosus. Autoimmun Rev. 2002;1(6):365–72.

    PubMed  CAS  Google Scholar 

  68. Negi VS, Tripathy NK, Misra R, Nityanand S. Antiendothelial cell antibodies in scleroderma correlate with severe digital ischemia and pulmonary arterial hypertension. J Rheumatol. 1998;25(3):462–6.

    PubMed  CAS  Google Scholar 

  69. Li MT, Ai J, Tian Z, et al. Prevalence of anti-endothelial cell antibodies in patients with pulmonary arterial hypertension associated with connective tissue diseases. Chin Med Sci J. 2010;25(1):27–31.

    PubMed  Google Scholar 

  70. Quismorio Jr FP, Sharma O, Koss M, et al. Immunopathologic and clinical studies in pulmonary hypertension associated with systemic lupus erythematosus. Semin Arthritis Rheum. 1984;13(4):349–59.

    PubMed  Google Scholar 

  71. Nakagawa N, Osanai S, Ide H, et al. Severe pulmonary hypertension associated with primary Sjogren’s syndrome. Intern Med. 2003;42(12):1248–52.

    PubMed  Google Scholar 

  72. Heath D, Yacoub M. Lung mast cells in plexogenic pulmonary arteriopathy. J Clin Pathol. 1991;44(12):1003–6.

    PubMed  CAS  Google Scholar 

  73. Tucker A, McMurtry IF, Alexander AF, Reeves JT, Grover RF. Lung mast cell density and distribution in chronically hypoxic animals. J Appl Physiol. 1977;42(2):174–8.

    PubMed  CAS  Google Scholar 

  74. Benoist C, Mathis D. Mast cells in autoimmune disease. Nature. 2002;420(6917):875–8.

    PubMed  CAS  Google Scholar 

  75. Satoh T, Kimura K, Okano Y, Hirakata M, Kawakami Y, Kuwana M. Lack of circulating autoantibodies to bone morphogenetic protein receptor-II or activin receptor-like kinase 1 in mixed connective tissue disease patients with pulmonary arterial hypertension. Rheumatology (Oxford). 2005;44(2):192–6.

    CAS  Google Scholar 

  76. Tamby MC, Humbert M, Guilpain P, et al. Antibodies to fibroblasts in idiopathic and ­scleroderma-associated pulmonary hypertension. Eur Respir J. 2006;28(4):799–807.

    PubMed  CAS  Google Scholar 

  77. Terrier B, Tamby MC, Camoin L, et al. Antifibroblast antibodies from systemic sclerosis patients bind to {alpha}-enolase and are associated with interstitial lung disease. Ann Rheum Dis. 2010;69(2):428–33.

    PubMed  CAS  Google Scholar 

  78. Quarck R, Nawrot T, Meyns B, Delcroix M. C-reactive protein: a new predictor of adverse outcome in pulmonary arterial hypertension. J Am Coll Cardiol. 2009;53(14):1211–8.

    PubMed  CAS  Google Scholar 

  79. Soon E, Holmes AM, Treacy CM, et al. Elevated levels of inflammatory cytokines predict survival in idiopathic and familial pulmonary arterial hypertension. Circulation. 2010;122(9):920–7.

    PubMed  CAS  Google Scholar 

  80. Otterdal K, Smith C, Oie E, et al. Platelet-derived LIGHT induces inflammatory responses in endothelial cells and monocytes. Blood. 2006;108(3):928–35.

    PubMed  CAS  Google Scholar 

  81. Otterdal K, Andreassen AK, Yndestad A, et al. Raised LIGHT levels in pulmonary arterial hypertension: potential role in thrombus formation. Am J Respir Crit Care Med. 2008;177(2):202–7.

    PubMed  CAS  Google Scholar 

  82. Heresi GA, Aytekin M, Newman J, Dweik RA. CXC-chemokine ligand 10 in idiopathic pulmonary arterial hypertension: marker of improved survival. Lung. 2010;188(3):191–7.

    PubMed  CAS  Google Scholar 

  83. Idzko M, Hammad H, van Nimwegen M, et al. Inhaled iloprost suppresses the cardinal features of asthma via inhibition of airway dendritic cell function. J Clin Invest. 2007;117(2):464–72.

    PubMed  CAS  Google Scholar 

  84. Jaffar Z, Ferrini ME, Buford MC, Fitzgerald GA, Roberts K. Prostaglandin I2-IP signaling blocks allergic pulmonary inflammation by preventing recruitment of CD4+ Th2 cells into the airways in a mouse model of asthma. J Immunol. 2007;179(9):6193–203.

    PubMed  CAS  Google Scholar 

  85. Zhou W, Hashimoto K, Goleniewska K, et al. Prostaglandin I2 analogs inhibit proinflammatory cytokine production and T cell stimulatory function of dendritic cells. J Immunol. 2007;178(2):702–10.

    PubMed  CAS  Google Scholar 

  86. Raychaudhuri B, Malur A, Bonfield TL, et al. The prostacyclin analogue treprostinil blocks NFkappaB nuclear translocation in human alveolar macrophages. J Biol Chem. 2002;277(36):33344–8.

    PubMed  CAS  Google Scholar 

  87. Zardi EM, Zardi DM, Cacciapaglia F, et al. Endothelial dysfunction and activation as an expression of disease: role of prostacyclin analogs. Int Immunopharmacol. 2005;5(3):437–59.

    PubMed  CAS  Google Scholar 

  88. Goya K, Otsuki M, Xu X, Kasayama S. Effects of the prostaglandin I2 analogue, beraprost sodium, on vascular cell adhesion molecule-1 expression in human vascular endothelial cells and circulating vascular cell adhesion molecule-1 level in patients with type 2 diabetes mellitus. Metabolism. 2003;52(2):192–8.

    PubMed  CAS  Google Scholar 

  89. Katsushi H, Kazufumi N, Hideki F, et al. Epoprostenol therapy decreases elevated circulating levels of monocyte chemoattractant protein-1 in patients with primary pulmonary hypertension. Circ J. 2004;68(3):227–31.

    PubMed  Google Scholar 

  90. Rose F, Hattar K, Gakisch S, et al. Increased neutrophil mediator release in patients with pulmonary hypertension–suppression by inhaled iloprost. Thromb Haemost. 2003;90(6):1141–9.

    PubMed  CAS  Google Scholar 

  91. Oudiz RJ, Farber HW. Dosing considerations in the use of intravenous prostanoids in pulmonary arterial hypertension: an experience-based review. Am Heart J. 2009;157(4):625–35.

    PubMed  CAS  Google Scholar 

  92. Aronoff DM, Peres CM, Serezani CH, et al. Synthetic prostacyclin analogs differentially regulate macrophage function via distinct analog-receptor binding specificities. J Immunol. 2007;178(3):1628–34.

    PubMed  CAS  Google Scholar 

  93. Browatzki M, Schmidt J, Kubler W, Kranzhofer R. Endothelin-1 induces interleukin-6 release via activation of the transcription factor NF-kappaB in human vascular smooth muscle cells. Basic Res Cardiol. 2000;95(2):98–105.

    PubMed  CAS  Google Scholar 

  94. Helset E, Lindal S, Olsen R, Myklebust R, Jorgensen L. Endothelin-1 causes sequential trapping of platelets and neutrophils in pulmonary microcirculation in rats. Am J Physiol. 1996;271(4 Pt 1):L538–46.

    PubMed  CAS  Google Scholar 

  95. Finsnes F, Skjonsberg OH, Tonnessen T, Naess O, Lyberg T, Christensen G. Endothelin production and effects of endothelin antagonism during experimental airway inflammation. Am J Respir Crit Care Med. 1997;155(4):1404–12.

    PubMed  CAS  Google Scholar 

  96. Finsnes F, Lyberg T, Christensen G, Skjonsberg OH. Effect of endothelin antagonism on the production of cytokines in eosinophilic airway inflammation. Am J Physiol Lung Cell Mol Physiol. 2001;280(4):L659–65.

    PubMed  CAS  Google Scholar 

  97. Verma S, Li SH, Badiwala MV, et al. Endothelin antagonism and interleukin-6 inhibition attenuate the proatherogenic effects of C-reactive protein. Circulation. 2002;105(16):1890–6.

    PubMed  CAS  Google Scholar 

  98. Uhlmann D, Gabel G, Ludwig S, et al. Effects of ET(A) receptor antagonism on proinflammatory gene expression and microcirculation following hepatic ischemia/reperfusion. Micro­circulation. 2005;12(5):405–19.

    PubMed  CAS  Google Scholar 

  99. Hauck EF, Hoffmann JF, Heimann A, Kempski O. EndothelinA receptor antagonist BSF-208075 causes immune modulation and neuroprotection after stroke in gerbils. Brain Res. 2007;1157:138–45.

    PubMed  CAS  Google Scholar 

  100. Guruli G, Pflug BR, Pecher S, Makarenkova V, Shurin MR, Nelson JB. Function and survival of dendritic cells depend on endothelin-1 and endothelin receptor autocrine loops. Blood. 2004;104(7):2107–15.

    PubMed  CAS  Google Scholar 

  101. Karavolias GK, Georgiadou P, Gkouziouta A, et al. Short and long term anti-inflammatory effects of bosentan therapy in patients with pulmonary arterial hypertension: relation to clinical and hemodynamic responses. Expert Opin Ther Targets. 2010;14(12):1283–9.

    PubMed  CAS  Google Scholar 

  102. Wang T, Liu Y, Chen L, et al. Effect of sildenafil on acrolein-induced airway inflammation and mucus production in rats. Eur Respir J. 2009;33(5):1122–32.

    PubMed  CAS  Google Scholar 

  103. Toward TJ, Smith N, Broadley KJ. Effect of phosphodiesterase-5 inhibitor, sildenafil (Viagra), in animal models of airways disease. Am J Respir Crit Care Med. 2004;169(2):227–34.

    PubMed  Google Scholar 

  104. Serafini P, Meckel K, Kelso M, et al. Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function. J Exp Med. 2006;203(12):2691–702.

    PubMed  CAS  Google Scholar 

  105. Shenoy P, Agarwal V. Phosphodiesterase inhibitors in the management of autoimmune disease. Autoimmun Rev. 2010;9(7):511–5.

    PubMed  CAS  Google Scholar 

  106. Dewar AL, Domaschenz RM, Doherty KV, Hughes TP, Lyons AB. Imatinib inhibits the in vitro development of the monocyte/macrophage lineage from normal human bone marrow progenitors. Leukemia. 2003;17(9):1713–21.

    PubMed  CAS  Google Scholar 

  107. Seggewiss R, Price DA, Purbhoo MA. Immunomodulatory effects of imatinib and second-generation tyrosine kinase inhibitors on T cells and dendritic cells: an update. Cytotherapy. 2008;10(6):633–41.

    PubMed  CAS  Google Scholar 

  108. Appel S, Boehmler AM, Grunebach F, et al. Imatinib mesylate affects the development and function of dendritic cells generated from CD34+ peripheral blood progenitor cells. Blood. 2004;103(2):538–44.

    PubMed  CAS  Google Scholar 

  109. Taieb J, Chaput N, Menard C, et al. A novel dendritic cell subset involved in tumor immunosurveillance. Nat Med. 2006;12(2):214–9.

    PubMed  CAS  Google Scholar 

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Supports

Frederic Perros and the team from the INSERM U999 unit are supported by FRM (Fondation pour la Recherche Médicale), team FRM 2010, grant DEQ20100318257.

Peter Dorfmüller and David Montani are supported by the Association HTAPFrance.

Author information

Authors and Affiliations

  1. Faculté de médecine, Univ. Paris-Sud, Kremlin-Bicêtre, Paris, France

    Frédéric Perros, Sylvia Cohen-Kaminsky, Peter Dorfmüller, Alice Huertas, Marie-Camille Chaumais, David Montani & Marc Humbert

  2. Service de Pneumologie et Réanimation Respiratoire, AP-HP, Centre National de Référence de l’Hypertension Pulmonaire Sévère, Hôpital Antoine Béclère, Clamart, France

    Frédéric Perros, Sylvia Cohen-Kaminsky, Peter Dorfmüller, Alice Huertas, David Montani & Marc Humbert

  3. INSERM U999, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, Le Plessis-Robinson, France

    Frédéric Perros, Sylvia Cohen-Kaminsky, Peter Dorfmüller, Alice Huertas, Marie-Camille Chaumais, David Montani & Marc Humbert

  4. Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France

    Frédéric Perros, Sylvia Cohen-Kaminsky, Peter Dorfmüller, Alice Huertas, Marie-Camille Chaumais, David Montani & Marc Humbert

  5. INSERM U999, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France

    Frédéric Perros

  6. Service de pharmacie, Hôpital Antoine Béclère, Assistance Publique des Hôpitaux de Paris, Clamart, France

    Marie-Camille Chaumais

Authors
  1. Frédéric Perros
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  2. Sylvia Cohen-Kaminsky
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  3. Peter Dorfmüller
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  4. Alice Huertas
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  5. Marie-Camille Chaumais
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  6. David Montani
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  7. Marc Humbert
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Corresponding author

Correspondence to Frédéric Perros .

Editor information

Editors and Affiliations

  1. University College London, Gower Street, London, WC1E 6BT, United Kingdom

    David Abraham

  2. The Royal Free & Univ College Med School, Gower Street, London, WC1E 6BT, United Kingdom

    Clive Handler

  3. University College London, Gower Street, London, WC1E 6BT, United Kingdom

    Michael Dashwood

  4. The Royal Free & Univ College Med School, Gower Street, London, WC1E 6BT, United Kingdom

    Gerry Coghlan

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© 2012 Springer-Verlag London Limited

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Perros, F. et al. (2012). Inflammation in Pulmonary Arterial Hypertension. In: Abraham, D., Handler, C., Dashwood, M., Coghlan, G. (eds) Translational Vascular Medicine. Springer, London. https://doi.org/10.1007/978-0-85729-920-8_14

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  • DOI: https://doi.org/10.1007/978-0-85729-920-8_14

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  • Publisher Name: Springer, London

  • Print ISBN: 978-0-85729-919-2

  • Online ISBN: 978-0-85729-920-8

  • eBook Packages: MedicineMedicine (R0)

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