Immune and inflammatory mechanisms in pulmonary arterial hypertension

Progress in Cardiovascular Diseases

Volumn 55, Issue 2, 2012, Pages 218-228

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

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

^b TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Cytokines; Growth factors; Immunity; Inflammation; Pulmonary arterial hypertension; Vascular remodeling

Indexed keywords

AUTOANTIBODY; CHEMOKINE; CYTOKINE; EPIDERMAL GROWTH FACTOR; FIBROBLAST GROWTH FACTOR; GROWTH FACTOR; HYPOXIA INDUCIBLE FACTOR 1; NEF PROTEIN; PLATELET DERIVED GROWTH FACTOR; PROTEIN TYROSINE KINASE; SEROTONIN; SEROTONIN TRANSPORTER; STAT PROTEIN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR NFAT; TRANSFORMING GROWTH FACTOR BETA1; VASOACTIVE INTESTINAL POLYPEPTIDE;

ANTIBODY RESPONSE; ARTICLE; CYTOKINE PRODUCTION; DISEASE ASSOCIATION; GENE DELETION; GENE EXPRESSION REGULATION; GENE OVEREXPRESSION; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; IMMUNOREACTIVITY; INFLAMMATION; MACROPHAGE ACTIVATION; MOLECULAR INTERACTION; MOLECULAR PATHOLOGY; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN TARGETING; PULMONARY HYPERTENSION; REGULATORY T LYMPHOCYTE; SIGNAL TRANSDUCTION; UPREGULATION;

ANIMALS; CHEMOKINES; HUMANS; HYPERTENSION, PULMONARY; IMMUNITY, INNATE; INFLAMMATION;

EID: 84866618858     PISSN: 00330620     EISSN: 18731740     Source Type: Journal    
DOI: 10.1016/j.pcad.2012.07.006     Document Type: Article

References (100)

1. Simonneau G., Robbins I.M., Beghetti M., et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2009, 54:S43-S54.
2. D'Alonzo G.E., Barst R.J., Ayres S.M., et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med 1991, 115:343-349.
3. Budhiraja R., Tuder R.M., Hassoun P.M. Endothelial dysfunction in pulmonary hypertension. Circulation 2004, 109:159-165.
4. Humbert M., Sitbon O., Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med 2004, 351:1425-1436.
5. Hassoun P.M., Mouthon L., Barbera J.A., et al. Inflammation, growth factors, and pulmonary vascular remodeling. J Am Coll Cardiol 2009, 54:S10-S19.
6. Isern R.A., Yaneva M., Weiner E., et al. Autoantibodies in patients with primary pulmonary hypertension: association with anti-Ku. Am J Med 1992, 93:307-312.
7. 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, 151:1628-1631.
8. Voelkel N.F., Cool C., Lee S.D., et al. Primary pulmonary hypertension between inflammation and cancer. Chest 1998, 114:225S-230S.
9. Nicolls M.R., Taraseviciene-Stewart L., Rai P.R., et al. Autoimmunity and pulmonary hypertension: a perspective. Eur Respir J 2005, 26:1110-1118.
10. Fartoukh M., Emilie D., Le Gall C., et al. Chemokine macrophage inflammatory protein-1alpha mRNA expression in lung biopsy specimens of primary pulmonary hypertension. Chest 1998, 114:50S-51S.
11. Sakamaki F., Kyotani S., Nagaya N., et al. Increased plasma P-selectin and decreased thrombomodulin in pulmonary arterial hypertension were improved by continuous prostacyclin therapy. Circulation 2000, 102:2720-2725.
12. Tuder R.M., Groves B., Badesch D.B., et al. Exuberant endothelial cell growth and elements of inflammation are present in plexiform lesions of pulmonary hypertension. Am J Pathol 1994, 144:275-285.
13. Dorfmuller P., Humbert M., Perros F., et al. Fibrous remodeling of the pulmonary venous system in pulmonary arterial hypertension associated with connective tissue diseases. Hum Pathol 2007, 38:893-902.
14. Balabanian K., Foussat A., Dorfmuller P., et al. CX(3)C chemokine fractalkine in pulmonary arterial hypertension. Am J Respir Crit Care Med 2002, 165:1419-1425.
15. Perros F., Dorfmuller P., Souza R., et al. Fractalkine-induced smooth muscle cell proliferation in pulmonary hypertension. Eur Respir J 2007, 29:937-943.
16. 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, 176:1041-1047.
17. Dorfmuller P., Zarka V., Durand-Gasselin I., et al. Chemokine RANTES in severe pulmonary arterial hypertension. Am J Respir Crit Care Med 2002, 165:534-539.
18. Selimovic N., Bergh C.H., Andersson B., et al. Growth factors and interleukin-6 across the lung circulation in pulmonary hypertension. Eur Respir J 2009, 34:662-668.
19. Chaouat A., Savale L., Chouaid C., et al. Role for interleukin-6 in COPD-related pulmonary hypertension. Chest 2009, 136:678-687.
20. Golembeski S.M., West J., Tada Y., et al. Interleukin-6 causes mild pulmonary hypertension and augments hypoxia-induced pulmonary hypertension in mice. Chest 2005, 128:572S-573S.
21. Steiner MK, Syrkina OL, Kolliputi N, et al. Interleukin-6 overexpression induces pulmonary hypertension. Circ Res 2009;104:236-244, 28p following 44.
22. 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.
23. Nishizuka Y., Sakakura T. Thymus and reproduction: sex-linked dysgenesia of the gonad after neonatal thymectomy in mice. Science 1969, 166:753-755.
24. Sakaguchi S., Takahashi T., Nishizuka Y. Study on cellular events in post-thymectomy autoimmune oophoritis in mice. II. Requirement of Lyt-1 cells in normal female mice for the prevention of oophoritis. J Exp Med 1982, 156:1577-1586.
25. Ulrich S., Nicolls M.R., Taraseviciene L., et al. Increased regulatory and decreased CD8+ cytotoxic T cells in the blood of patients with idiopathic pulmonary arterial hypertension. Respiration 2008, 75:272-280.
26. Tamosiuniene R., Tian W., Dhillon G., et al. Regulatory T cells limit vascular endothelial injury and prevent pulmonary hypertension. Circ Res 2011, 109:867-879.
27. Humbert M., Monti G., Fartoukh M., et al. Platelet-derived growth factor expression in primary pulmonary hypertension: comparison of HIV seropositive and HIV seronegative patients. Eur Respir J 1998, 11:554-559.
28. Schermuly R.T., Dony E., Ghofrani H.A., et al. Reversal of experimental pulmonary hypertension by PDGF inhibition. J Clin Invest 2005, 115:2811-2821.
29. Wedgwood S., Devol J.M., Grobe A., et al. Fibroblast growth factor-2 expression is altered in lambs with increased pulmonary blood flow and pulmonary hypertension. Pediatr Res 2007, 61:32-36.
30. Merklinger S.L., Jones P.L., Martinez E.C., et al. Epidermal growth factor receptor blockade mediates smooth muscle cell apoptosis and improves survival in rats with pulmonary hypertension. Circulation 2005, 112:423-431.
31. Sakao S., Taraseviciene-Stewart L., Cool C.D., et al. 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 2007, 21:3640-3652.
32. Taraseviciene-Stewart L., Scerbavicius R., Choe K.H., et al. Simvastatin causes endothelial cell apoptosis and attenuates severe pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 2006, 291:L668-L676.
33. Christou H., Yoshida A., Arthur V., et al. Increased vascular endothelial growth factor production in the lungs of rats with hypoxia-induced pulmonary hypertension. Am J Respir Cell Mol Biol 1998, 18:768-776.
34. Cool C.D., Stewart J.S., Werahera P., et al. 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 1999, 155:411-419.
35. Tuder R.M., Cool C.D., Yeager M., et al. The pathobiology of pulmonary hypertension. Endothelium. Clin Chest Med 2001, 22:405-418.
36. Tuder R.M., Flook B.E., Voelkel N.F. Increased gene expression for VEGF 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 1995, 95:1798-1807.
37. 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.
38. Klein M., Schermuly R.T., Ellinghaus P., et al. Combined tyrosine and serine/threonine kinase inhibition by sorafenib prevents progression of experimental pulmonary hypertension and myocardial remodeling. Circulation 2008, 118:2081-2090.
39. Balasubramaniam V., Le Cras T.D., Ivy D.D., et al. Role of platelet-derived growth factor in vascular remodeling during pulmonary hypertension in the ovine fetus. Am J Physiol Lung Cell Mol Physiol 2003, 284:L826-L833.
40. Morrell N.W. Pulmonary hypertension due to BMPR2 mutation: a new paradigm for tissue remodeling?. Proc Am Thorac Soc 2006, 3:680-686.
41. Trembath R.C., Thomson J.R., Machado R.D., et al. Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia. N Engl J Med 2001, 345:325-334.
42. Yeager M.E., Halley G.R., Golpon H.A., et al. Microsatellite instability of endothelial cell growth and apoptosis genes within plexiform lesions in primary pulmonary hypertension. Circ Res 2001, 88:E2-E11.
43. Zaiman A.L., Podowski M., Medicherla S., et al. Role of the TGF-beta/Alk5 signaling pathway in monocrotaline-induced pulmonary hypertension. Am J Respir Crit Care Med 2008, 177:896-905.
44. Quinn T.P., Schlueter M., Soifer S.J., et al. Cyclic mechanical stretch induces VEGF and FGF-2 expression in pulmonary vascular smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 2002, 282:L897-L903.
45. Jones P.L., 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 1996, 79:1131-1142.
46. Jones P.L., Cowan K.N., Rabinovitch M. Tenascin-C, proliferation and subendothelial fibronectin in progressive pulmonary vascular disease. Am J Pathol 1997, 150:1349-1360.
47. Henning R.J., Sawmiller D.R. Vasoactive intestinal peptide: cardiovascular effects. Cardiovasc Res 2001, 49:27-37.
48. Petkov V., Mosgoeller W., Ziesche R., et al. Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension. J Clin Invest 2003, 111:1339-1346.
49. Janosi T., Petak F., Fontao F., et al. 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 2008, 93:1210-1219.
50. Cox C.P., Linden J., Said S.I. VIP elevates platelet cyclic AMP (cAMP) levels and inhibits in vitro platelet activation induced by platelet-activating factor (PAF). Peptides 1984, 5:325-328.
51. Hamidi S.A., Prabhakar S., Said S.I. Enhancement of pulmonary vascular remodelling and inflammatory genes with VIP gene deletion. Eur Respir J 2008, 31:135-139.
52. Said S.I., Hamidi S.A., Dickman K.G., et al. Moderate pulmonary arterial hypertension in male mice lacking the vasoactive intestinal peptide gene. Circulation 2007, 115:1260-1268.
53. Vuckovic A., Rondelet B., Brion J.P., et al. Expression of vasoactive intestinal peptide and related receptors in overcirculation-induced pulmonary hypertension in piglets. Pediatr Res 2009, 66:395-399.
54. Leuchte H.H., Baezner C., Baumgartner R.A., et al. Inhalation of vasoactive intestinal peptide in pulmonary hypertension. Eur Respir J 2008, 32:1289-1294.
55. MacLean M.R., Herve P., Eddahibi S., et al. 5-hydroxytryptamine and the pulmonary circulation: receptors, transporters and relevance to pulmonary arterial hypertension. Br J Pharmacol 2000, 131:161-168.
56. Lee S.L., Wang W.W., Moore B.J., et al. Dual effect of serotonin on growth of bovine pulmonary artery smooth muscle cells in culture. Circ Res 1991, 68:1362-1368.
57. Eddahibi S., Fabre V., Boni C., et al. Induction of serotonin transporter by hypoxia in pulmonary vascular smooth muscle cells. Relationship with the mitogenic action of serotonin. Circ Res 1999, 84:329-336.
58. Fanburg B.L., Lee S.L. A new role for an old molecule: serotonin as a mitogen. Am J Physiol 1997, 272:L795-L806.
59. Eddahibi S., Humbert M., Fadel E., et al. Hyperplasia of pulmonary artery smooth muscle cells is causally related to overexpression of the serotonin transporter in primary pulmonary hypertension. Chest 2002, 121:97S-98S.
60. Eddahibi S., Humbert M., Fadel E., et al. Serotonin transporter overexpression is responsible for pulmonary artery smooth muscle hyperplasia in primary pulmonary hypertension. J Clin Invest 2001, 108:1141-1150.
61. Eddahibi S., Hanoun N., Lanfumey L., et al. Attenuated hypoxic pulmonary hypertension in mice lacking the 5-hydroxytryptamine transporter gene. J Clin Invest 2000, 105:1555-1562.
62. Guignabert C., Raffestin B., Benferhat R., et al. Serotonin transporter inhibition prevents and reverses monocrotaline-induced pulmonary hypertension in rats. Circulation 2005, 111:2812-2819.
63. Crona D., Harral J., Adnot S., et al. Gene expression in lungs of mice lacking the 5-hydroxytryptamine transporter gene. BMC Pulm Med 2009, 9:19.
64. MacLean M.R., Deuchar G.A., Hicks M.N., et al. Overexpression of the 5-hydroxytryptamine transporter gene: effect on pulmonary hemodynamics and hypoxia-induced pulmonary hypertension. Circulation 2004, 109:2150-2155.
65. Guignabert C., Izikki M., Tu L.I., et al. Transgenic mice overexpressing the 5-hydroxytryptamine transporter gene in smooth muscle develop pulmonary hypertension. Circ Res 2006, 98:1323-1330.
66. Dempsie Y., Morecroft I., Welsh D.J., et al. Converging Evidence in Support of the Serotonin Hypothesis of Dexfenfluramine-Induced Pulmonary Hypertension With Novel Transgenic Mice. Circulation 2008, 117:2928-2937.
67. Macian F. NFAT proteins: key regulators of T-cell development and function. Nat Rev Immunol 2005, 5:472-484.
68. Rossow C.F., Minami E., Chase E.G., et al. NFATc3-induced reductions in voltage-gated K+ currents after myocardial infarction. Circ Res 2004, 94:1340-1350.
69. Kawamura T., Ono K., Morimoto T., et al. 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 2004, 94:1492-1499.
70. Bushdid P.B., Osinska H., Waclaw R.R., et al. NFATc3 and NFATc4 are required for cardiac development and mitochondrial function. Circ Res 2003, 92:1305-1313.
71. Bonnet S., Rochefort G., Sutendra G., et al. The nuclear factor of activated T cells in pulmonary arterial hypertension can be therapeutically targeted. Proc Natl Acad Sci U S A 2007, 104:11418-11423.
72. Michelakis E.D., McMurtry M.S., Wu X.C., et al. 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 2002, 105:244-250.
73. Archer S.L., Gomberg-Maitland M., Maitland M.L., et al. 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 2008, 294:H570-H578.
74. Bonnet S., Michelakis E.D., Porter C.J., et al. 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 2006, 113:2630-2641.
75. Kentera D., Susic D., Veljkovic V., et al. Pulmonary artery pressure in rats with hereditary platelet function defect. Respiration 1988, 54:110-114.
76. Wang G.S., Qian G.S., Bai L., et al. Enhanced expression of signal transducers and activators of transcription in lung tissue of hypoxic pulmonary hypertension rat models. Zhonghua Nei Ke Za Zhi 2003, 42:768-772.
77. Aaronson D.S., Horvath C.M. A road map for those who don't know JAK-STAT. Science 2002, 296:1653-1655.
78. Kawamura C., Kizaki M., Yamato K., et al. Bone morphogenetic protein-2 induces apoptosis in human myeloma cells with modulation of STAT3. Blood 2000, 96:2005-2011.
79. Xu W., Comhair S.A., Zheng S., et al. STAT-1 and c-Fos interaction in nitric oxide synthase-2 gene activation. Am J Physiol Lung Cell Mol Physiol 2003, 285:L137-L148.
80. Xu W., Kaneko F.T., Zheng S., et al. Increased arginase II and decreased NO synthesis in endothelial cells of patients with pulmonary arterial hypertension. FASEB J 2004, 18:1746-1748.
81. Masri F.A., Xu W., Comhair S.A., et al. Hyperproliferative apoptosis-resistant endothelial cells in idiopathic pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol 2007, 293:L548-L554.
82. Mette S.A., Palevsky H.I., Pietra G.G., et al. 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 1992, 145:1196-1200.
83. Humbert M. Mediators involved in HIV-related pulmonary arterial hypertension. AIDS 2008, 22(Suppl. 3):S41-S47.
84. Ehrenreich H., Rieckmann P., Sinowatz F., et al. Potent stimulation of monocytic endothelin-1 production by HIV-1 glycoprotein 120. J Immunol 1993, 150:4601-4609.
85. Marecki J.C., Cool C.D., Parr J.E., et al. HIV-1 Nef is associated with complex pulmonary vascular lesions in SHIV-nef-infected macaques. Am J Respir Crit Care Med 2006, 174:437-445.
86. Ali S.A., Huang M.B., Campbell P.E., et al. Genetic characterization of HIV type 1 Nef-induced vesicle secretion. AIDS Res Hum Retroviruses 2010, 26:173-192.
87. Lundquist C.A., Tobiume M., Zhou J., et al. Nef-mediated downregulation of CD4 enhances human immunodeficiency virus type 1 replication in primary T lymphocytes. J Virol 2002, 76:4625-4633.
88. Swann S.A., Williams M., Story C.M., et al. HIV-1 Nef blocks transport of MHC class I molecules to the cell surface via a PI 3-kinase-dependent pathway. Virology 2001, 282:267-277.
89. Collins K.L., Chen B.K., Kalams S.A., et al. HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes. Nature 1998, 391:397-401.
90. Olivetta E., Percario Z., Fiorucci G., et al. HIV-1 Nef induces the release of inflammatory factors from human monocyte/macrophages: involvement of Nef endocytotic signals and NF-kappa B activation. J Immunol 2003, 170:1716-1727.
91. Okano Y., Steen V.D., Medsger T.A. Autoantibody to U3 nucleolar ribonucleoprotein (fibrillarin) in patients with systemic sclerosis. Arthritis Rheum 1992, 35:95-100.
92. Negi V.S., Tripathy N.K., Misra R., et al. Antiendothelial cell antibodies in scleroderma correlate with severe digital ischemia and pulmonary arterial hypertension. J Rheumatol 1998, 25:462-466.
93. Fritzler M.J., Hart D.A., Wilson D., et al. Antibodies to fibrin bound tissue type plasminogen activator in systemic sclerosis. J Rheumatol 1995, 22:1688-1693.
94. Morse J.H., Barst R.J., Fotino M., et al. Primary pulmonary hypertension, tissue plasminogen activator antibodies, and HLA-DQ7. Am J Respir Crit Care Med 1997, 155:274-278.
95. Grigolo B., Mazzetti I., Meliconi R., et al. Anti-topoisomerase II alpha autoantibodies in systemic sclerosis-association with pulmonary hypertension and HLA-B35. Clin Exp Immunol 2000, 121:539-543.
96. Okawa-Takatsuji M., Aotsuka S., Fujinami M., et al. 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 1999, 116:174-180.
97. Tamby M.C., Chanseaud Y., Humbert M., et al. Anti-endothelial cell antibodies in idiopathic and systemic sclerosis associated pulmonary arterial hypertension. Thorax 2005, 60:765-772.
98. Chizzolini C., Raschi E., Rezzonico R., et al. Autoantibodies to fibroblasts induce a proadhesive and proinflammatory fibroblast phenotype in patients with systemic sclerosis. Arthritis Rheum 2002, 46:1602-1613.
99. Tamby M.C., Humbert M., Guilpain P., et al. Antibodies to fibroblasts in idiopathic and scleroderma-associated pulmonary hypertension. Eur Respir J 2006, 28:799-807.
100. Terrier B., Tamby M.C., Camoin L., et al. Identification of target antigens of antifibroblast antibodies in pulmonary arterial hypertension. Am J Respir Crit Care Med 2008, 177:1128-1134.