Leukotriene B4 Activates Pulmonary Artery Adventitial Fibroblasts in Pulmonary Hypertension

Hypertension

Volumn 66, Issue 6, 2015, Pages 1227-1239

  Qian, Jin ^a   Tian, Wen ^a   Jiang, Xinguo ^a   Tamosiuniene, Rasa ^a   Sung, Yon K ^a   Shuffle, Eric M ^a   Tu, Allen B ^a   Valenzuela, Antonia ^a   Jiang, Shirley ^a   Zamanian, Roham T ^a   Fiorentino, David F ^a   Voelkel, Norbert F ^b   Peters Golden, Marc ^c   Stenmark, Kurt R ^d   Chung, Lorinda ^a   Rabinovitch, Marlene ^a   Nicolls, Mark R ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

^c UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^d Nutrition Obesity Research Center at the University of Colorado   (United States)

Author keywords

fibroblasts; inflammation; leukotriene B4; NADPH oxidase; p38 mitogen activated protein kinases; pulmonary artery; vascular remodeling

Indexed keywords

ALPHA SMOOTH MUSCLE ACTIN; AMINO TERMINAL PRO BRAIN NATRIURETIC PEPTIDE; CALVASCULIN; CD68 ANTIGEN; CHEMOKINE RECEPTOR CCR2; CHEMOKINE RECEPTOR CX3CR1; CYCLINE; G PROTEIN COUPLED RECEPTOR; HYDROGEN PEROXIDE; LEUKOTRIENE B4; LEUKOTRIENE B4 RECEPTOR; LEUKOTRIENE B4 RECEPTOR 1; MITOGEN ACTIVATED PROTEIN KINASE P38; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 4; TRANSFORMING GROWTH FACTOR ALPHA; UNCLASSIFIED DRUG; 4 (4 FLUOROPHENYL) 2 (4 METHYLSULFINYLPHENYL) 5 (4 PYRIDYL)IMIDAZOLE; ARACHIDONATE 5 LIPOXYGENASE; CHEMOKINE; ENZYME INHIBITOR; IMIDAZOLE DERIVATIVE; NOX4 PROTEIN, HUMAN; PYRIDINE DERIVATIVE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; TUMOR NECROSIS FACTOR;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CARDIOPULMONARY HEMODYNAMICS; CARDIOVASCULAR MORTALITY; CATALYSIS; CELL ACTIVATION; CELL COUNT; CELL DIFFERENTIATION; CELL EXPANSION; CELL MIGRATION; CELL PROLIFERATION; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; DISEASE COURSE; ENDOTHELIUM CELL; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; HEART RIGHT VENTRICLE HYPERTROPHY; HEART VENTRICLE WALL; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; LIPOGENESIS; LUNG FIBROBLAST; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PULMONARY HYPERTENSION; PULMONARY VASCULITIS; RAT; SIGNAL TRANSDUCTION; SMOOTH MUSCLE FIBER; SYSTOLIC BLOOD PRESSURE; UPREGULATION; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL CULTURE; CELL MOTION; CONFOCAL MICROSCOPY; DOSE RESPONSE; DRUG EFFECTS; FIBROBLAST; GENE EXPRESSION; GENETICS; METABOLISM; NUDE RAT; PATHOLOGY; PULMONARY ARTERY; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION;

ANIMALS; ARACHIDONATE 5-LIPOXYGENASE; CELL DIFFERENTIATION; CELL MOVEMENT; CELL PROLIFERATION; CELLS, CULTURED; CHEMOKINES; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME INHIBITORS; FIBROBLASTS; GENE EXPRESSION; HUMANS; HYPERTENSION, PULMONARY; IMIDAZOLES; LEUKOTRIENE B4; MICROSCOPY, CONFOCAL; NADPH OXIDASE; P38 MITOGEN-ACTIVATED PROTEIN KINASES; PULMONARY ARTERY; PYRIDINES; RATS, NUDE; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; TUMOR NECROSIS FACTOR-ALPHA;

EID: 84947492704     PISSN: 0194911X     EISSN: 15244563     Source Type: Journal    
DOI: 10.1161/HYPERTENSIONAHA.115.06370     Document Type: Article

References (66)

1. Sung YK, Chung L. Connective tissue disease-associated pulmonary arterial hypertension. Rheum Dis Clin North Am. 2015;41:295-313. doi: 10.1016/j.rdc.2015.01.003.
2. Lai YC, Potoka KC, Champion HC, Mora AL, Gladwin MT. Pulmonary arterial hypertension: the clinical syndrome. Circ Res. 2014;115:115-130. doi: 10.1161/CIRCRESAHA.115.301146.
3. Zamanian RT, Kudelko KT, Sung YK, de Jesus Perez V, Liu J, Spiekerkoetter E. Current clinical management of pulmonary arterial hypertension. Circ Res. 2014;115:131-147. doi: 10.1161/CIRCRESAHA.115.303827.
4. McLaughlin VV, Shah SJ, Souza R, Humbert M. Management of pulmonary arterial hypertension. J Am Coll Cardiol. 2015;65:1976-1997. doi: 10.1016/j.jacc.2015.03.540.
5. Humbert M, Lau EM, Montani D, Jaïs X, Sitbon O, Simonneau G. Advances in therapeutic interventions for patients with pulmonary arterial hypertension. Circulation. 2014;130:2189-2208. doi: 10.1161/CIRCULATIONAHA.114.006974.
6. Burke DL, Frid MG, Kunrath CL, Karoor V, Anwar A, Wagner BD, Strassheim D, Stenmark KR. Sustained hypoxia promotes the development of a pulmonary artery-specific chronic inflammatory microenvironment. Am J Physiol Lung Cell Mol Physiol. 2009;297:L238-L250. doi: 10.1152/ajplung.90591.2008.
7. Rabinovitch M, Guignabert C, Humbert M, Nicolls MR. Inflammation and immunity in the pathogenesis of pulmonary arterial hypertension. Circ Res. 2014;115:165-175. doi: 10.1161/CIRCRESAHA.113.301141.
8. Guignabert C, Tu L, Girerd B, Ricard N, Huertas A, Montani D, Humbert M. New molecular targets of pulmonary vascular remodeling in pulmonary arterial hypertension: importance of endothelial communication. Chest. 2015;147:529-537. doi: 10.1378/chest.14-0862.
9. Archer SL, Weir EK, Wilkins MR. Basic science of pulmonary arterial hypertension for clinicians: new concepts and experimental therapies. Circulation. 2010;121:2045-2066. doi: 10.1161/CIRCULATIONAHA.108.847707.
10. Tian W, Jiang X, Tamosiuniene R, Sung YK, Qian J, Dhillon G, Gera L, Farkas L, Rabinovitch M, Zamanian RT, Inayathullah M, Fridlib M, Rajadas J, Peters-Golden M, Voelkel NF, Nicolls MR. Blocking macrophage leukotriene b4 prevents endothelial injury and reverses pulmonary hypertension. Sci Transl Med. 2013;5:200ra117. doi: 10.1126/scitranslmed.3006674.
11. Tuder RM, Marecki JC, Richter A, Fijalkowska I, Flores S. Pathology of pulmonary hypertension. Clin Chest Med. 2007;28:23-42, vii. doi: 10.1016/j.ccm.2006.11.010.
12. Stenmark KR, Frid MG, Yeager M, Li M, Riddle S, McKinsey T, El Kasmi KC. Targeting the adventitial microenvironment in pulmonary hypertension: a potential approach to therapy that considers epigenetic change. Pulm Circ. 2012;2:3-14. doi: 10.4103/2045-8932.94817.
13. Stenmark KR, Davie N, Frid M, Gerasimovskaya E, Das M. Role of the adventitia in pulmonary vascular remodeling. Physiology (Bethesda). 2006;21:134-145. doi: 10.1152/physiol.00053.2005.
14. Stenmark KR, Nozik-Grayck E, Gerasimovskaya E, Anwar A, Li M, Riddle S, Frid M. The adventitia: essential role in pulmonary vascular remodeling. Compr Physiol. 2011;1:141-161. doi: 10.1002/cphy. c090017.
15. Stenmark KR, Yeager ME, El Kasmi KC, Nozik-Grayck E, Gerasimovskaya EV, Li M, Riddle SR, Frid MG. The adventitia: essential regulator of vascular wall structure and function. Annu Rev Physiol. 2013;75:23-47. doi: 10.1146/annurev-physiol-030212-183802.
16. Stenmark KR, Fagan KA, Frid MG. Hypoxia-induced pulmonary vascular remodeling: cellular and molecular mechanisms. Circ Res. 2006;99:675-691. doi: 10.1161/01.RES.0000243584.45145.3f.
17. Carlin CM, Peacock AJ, Welsh DJ. Fluvastatin inhibits hypoxic proliferation and p38 MAPK activity in pulmonary artery fibroblasts. Am J Respir Cell Mol Biol. 2007;37:447-456. doi: 10.1165/rcmb.2007-0012OC.
18. Welsh DJ, Peacock AJ, MacLean M, Harnett M. Chronic hypoxia induces constitutive p38 mitogen-activated protein kinase activity that correlates with enhanced cellular proliferation in fibroblasts from rat pulmonary but not systemic arteries. Am J Respir Crit Care Med. 2001;164:282-289. doi: 10.1164/ajrccm.164.2.2008054.
19. Welsh DJ, Scott PH, Peacock AJ. p38 MAP kinase isoform activity and cell cycle regulators in the proliferative response of pulmonary and systemic artery fibroblasts to acute hypoxia. Pulm Pharmacol Ther. 2006;19:128-138. doi: 10.1016/j.pupt.2005.04.008.
20. Barman SA, Chen F, Su Y, et al. NADPH oxidase 4 is expressed in pulmonary artery adventitia and contributes to hypertensive vascular remodeling. Arterioscler Thromb Vasc Biol. 2014;34:1704-1715. doi: 10.1161/ATVBAHA.114.303848.
21. Li M, Riddle SR, Frid MG, et al. Emergence of fibroblasts with a proinflammatory epigenetically altered phenotype in severe hypoxic pulmonary hypertension. J Immunol. 2011;187:2711-2722. doi: 10.4049/jimmunol.1100479.
22. Panzhinskiy E, Zawada WM, Stenmark KR, Das M. Hypoxia induces unique proliferative response in adventitial fibroblasts by activating PDGFβ receptor-JNK1 signalling. Cardiovasc Res. 2012;95:356-365. doi: 10.1093/cvr/cvs194.
23. Das M, Burns N, Wilson SJ, Zawada WM, Stenmark KR. Hypoxia exposure induces the emergence of fibroblasts lacking replication repressor signals of PKC zeta in the pulmonary artery adventitia. Cardiovasc Res. 2008;78:440-448. doi: 10.1093/cvr/cvn014.
24. Zarubin T, Han J. Activation and signaling of the p38 MAP kinase pathway. Cell Res. 2005;15:11-18. doi: 10.1038/sj.cr.7290257.
25. Fisk M, Gajendragadkar PR, Mäki-Petäjä KM, Wilkinson IB, Cheriyan J. Therapeutic potential of p38 MAP kinase inhibition in the management of cardiovascular disease. Am J Cardiovasc Drugs. 2014;14:155-165. doi: 10.1007/s40256-014-0063-6.
26. Weerackody RP, Welsh DJ, Wadsworth RM, Peacock AJ. Inhibition of p38 MAPK reverses hypoxia-induced pulmonary artery endothelial dysfunction. Am J Physiol Heart Circ Physiol. 2009;296:H1312-H1320. doi: 10.1152/ajpheart.00977.2008.
27. Brown DI, Griendling KK. Nox proteins in signal transduction. Free Radic Biol Med. 2009;47:1239-1253. doi: 10.1016/j.freeradbiomed.2009.07.023.
28. Taverne YJ, Bogers AJ, Duncker DJ, Merkus D. Reactive oxygen species and the cardiovascular system. Oxid Med Cell Longev. 2013;2013:862423. doi: 10.1155/2013/862423.
29. Aggarwal S, Gross CM, Sharma S, Fineman JR, Black SM. Reactive oxygen species in pulmonary vascular remodeling. Compr Physiol. 2013;3:1011-1034. doi: 10.1002/cphy.c120024.
30. Park S, Ahn JY, Lim MJ, Kim MH, Yun YS, Jeong G, Song JY. Sustained expression of NADPH oxidase 4 by p38 MAPK-Akt signaling potentiates radiation-induced differentiation of lung fibroblasts. J Mol Med (Berl). 2010;88:807-816. doi: 10.1007/s00109-010-0622-5.
31. Peters-Golden M, Brock TG. 5-lipoxygenase and FLAP. Prostaglandins Leukot Essent Fatty Acids. 2003;69:99-109.
32. Israel E, Rubin P, Kemp JP, et al. The effect of inhibition of 5-lipoxygenase by zileuton in mild-to-moderate asthma. Ann Intern Med. 1993;119:1059-1066.
33. Spanbroek R, Grabner R, Lotzer K, et al. Expanding expression of the 5-lipoxygenase pathway within the arterial wall during human atherogenesis. Proc Natl Acad Sci U S A. 2003;100:1238-1243. doi: 10.1073/pnas.242716099.
34. Helgadottir A, Manolescu A, Thorleifsson G, et al. The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke. Nat Genet. 2004;36:233-239. doi: 10.1038/ng1311.
35. Helgadottir A, Manolescu A, Helgason A, et al. A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction. Nat Genet. 2006;38:68-74. doi: 10.1038/ng1692.
36. Tamosiuniene R, Tian W, Dhillon G, Wang L, Sung YK, Gera L, Patterson AJ, Agrawal R, Rabinovitch M, Ambler K, Long CS, Voelkel NF, Nicolls MR. Regulatory T cells limit vascular endothelial injury and prevent pulmonary hypertension. Circ Res. 2011;109:867-879. doi: 10.1161/CIRCRESAHA.110.236927.
37. Prasadam I, Mao X, Wang Y, Shi W, Crawford R, Xiao Y. Inhibition of p38 pathway leads to OA-like changes in a rat animal model. Rheumatology (Oxford). 2012;51:813-823. doi: 10.1093/rheumatology/ker360.
38. Chen XL, Xia ZF, Yu YX, Wei D, Wang CR, Ben DF. p38 mitogenactivated protein kinase inhibition attenuates burn-induced liver injury in rats. Burns. 2005;31:320-330. doi: 10.1016/j.burns.2004.10.015.
39. Qian J, Chen F, Kovalenkov Y, Pandey D, Moseley MA, Foster MW, Black SM, Venema RC, Stepp DW, Fulton DJ. Nitric oxide reduces NADPH oxidase 5 (Nox5) activity by reversible S-nitrosylation. Free Radic Biol Med. 2012;52:1806-1819. doi: 10.1016/j.freeradbiomed.2012.02.029.
40. El Kasmi KC, Pugliese SC, Riddle SR, et al. Adventitial fibroblasts induce a distinct proinflammatory/profibrotic macrophage phenotype in pulmonary hypertension. J Immunol. 2014;193:597-609. doi: 10.4049/jimmunol.1303048.
41. Pannu J, Asano Y, Nakerakanti S, Smith E, Jablonska S, Blaszczyk M, ten Dijke P, Trojanowska M. Smad1 pathway is activated in systemic sclerosis fibroblasts and is targeted by imatinib mesylate. Arthritis Rheum. 2008;58:2528-2537. doi: 10.1002/art.23698.
42. Badesch DB, Raskob GE, Elliott CG, Krichman AM, Farber HW, Frost AE, Barst RJ, Benza RL, Liou TG, Turner M, Giles S, Feldkircher K, Miller DP, McGoon MD. Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest. 2010;137:376-387. doi: 10.1378/chest.09-1140.
43. Denton CP, Black CM. Pulmonary hypertension in systemic sclerosis. Rheum Dis Clin North Am. 2003;29:335-49, vii.
44. Forte A, Della Corte A, De Feo M, Cerasuolo F, Cipollaro M. Role of myofibroblasts in vascular remodelling: focus on restenosis and aneurysm. Cardiovasc Res. 2010;88:395-405. doi: 10.1093/cvr/cvq224.
45. Kumar S, Jiang MS, Adams JL, Lee JC. Pyridinylimidazole compound SB 203580 inhibits the activity but not the activation of p38 mitogen-activated protein kinase. Biochem Biophys Res Commun. 1999;263:825-831. doi: 10.1006/bbrc.1999.1454.
46. Werz O, Klemm J, Samuelsson B, Rådmark O. 5-lipoxygenase is phosphorylated by p38 kinase-dependent MAPKAP kinases. Proc Natl Acad Sci U S A. 2000;97:5261-5266. doi: 10.1073/pnas.050588997.
47. Ito K, Hirao A, Arai F, Takubo K, Matsuoka S, Miyamoto K, Ohmura M, Naka K, Hosokawa K, Ikeda Y, Suda T. Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat Med. 2006;12:446-451. doi: 10.1038/nm1388.
48. Zuo L, Rose BA, Roberts WJ, He F, Banes-Berceli AK. Molecular characterization of reactive oxygen species in systemic and pulmonary hypertension. Am J Hypertens. 2014;27:643-650. doi: 10.1093/ajh/hpt292.
49. Nozik-Grayck E, Stenmark KR. Role of reactive oxygen species in chronic hypoxia-induced pulmonary hypertension and vascular remodeling. Adv Exp Med Biol. 2007;618:101-112.
50. Brock TG, Lee YJ, Maydanski E, Marburger TL, Luo M, Paine R III, Peters-Golden M. Nuclear localization of leukotriene A4 hydrolase in type II alveolar epithelial cells in normal and fibrotic lung. Am J Physiol Lung Cell Mol Physiol. 2005;289:L224-L232. doi: 10.1152/ajplung.00423.2004.
51. Ochiya T, Takenaga K, Endo H. Silencing of S100A4, a metastasis-associated protein, in endothelial cells inhibits tumor angiogenesis and growth. Angiogenesis. 2014;17:17-26. doi: 10.1007/s10456-013-9372-7.
52. Varga J, Abraham D. Systemic sclerosis: a prototypic multisystem fibrotic disorder. J Clin Invest. 2007;117:557-567. doi: 10.1172/JCI31139.
53. Yaqub A, Chung L. Epidemiology and risk factors for pulmonary hypertension in systemic sclerosis. Curr Rheumatol Rep. 2013;15:302. doi: 10.1007/s11926-012-0302-2.
54. Rådmark O, Samuelsson B. Regulation of the activity of 5-lipoxygenase, a key enzyme in leukotriene biosynthesis. Biochem Biophys Res Commun. 2010;396:105-110. doi: 10.1016/j.bbrc.2010.02.173.
55. Steiner MK, Syrkina OL, Kolliputi N, Mark EJ, Hales CA, Waxman AB. Interleukin-6 overexpression induces pulmonary hypertension. Circ Res. 2009;104:236-244. doi: 10.1161/CIRCRESAHA.108.182014.
56. Ishihara K, Hirano T. IL-6 in autoimmune disease and chronic inflammatory proliferative disease. Cytokine Growth Factor Rev. 2002;13:357-368.
57. Kaiser RA, Lyons JM, Duffy JY, Wagner CJ, McLean KM, O'Neill TP, Pearl JM, Molkentin JD. Inhibition of p38 reduces myocardial infarction injury in the mouse but not pig after ischemia-reperfusion. Am J Physiol Heart Circ Physiol. 2005;289:H2747-H2751. doi: 10.1152/ajpheart.01280.2004.
58. Ma XL, Kumar S, Gao F, Louden CS, Lopez BL, Christopher TA, Wang C, Lee JC, Feuerstein GZ, Yue TL. Inhibition of p38 mitogen-activated protein kinase decreases cardiomyocyte apoptosis and improves cardiac function after myocardial ischemia and reperfusion. Circulation. 1999;99:1685-1691.
59. Liu YH, Wang D, Rhaleb NE, Yang XP, Xu J, Sankey SS, Rudolph AE, Carretero OA. Inhibition of p38 mitogen-activated protein kinase protects the heart against cardiac remodeling in mice with heart failure resulting from myocardial infarction. J Card Fail. 2005;11:74-81.
60. Newby LK, Marber MS, Melloni C, et al; SOLSTICE Investigators. Losmapimod, a novel p38 mitogen-activated protein kinase inhibitor, in non-ST-segment elevation myocardial infarction: a randomised phase 2 trial. Lancet. 2014;384:1187-1195. doi: 10.1016/S0140-6736(14)60417-7.
61. Church AC, Martin DH, Wadsworth RM, Bryson G, Fisher AJ, Welsh DJ, Peacock AJ. The reversal of pulmonary vascular remodelling through inhibition of p38mapk-alpha: a potential novel anti-inflammatory strategy in pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2015:ajplung 00038 02015.
62. Brieger K, Schiavone S, Miller FJ Jr, Krause KH. Reactive oxygen species: from health to disease. Swiss Med Wkly. 2012;142:w13659. doi: 10.4414/smw.2012.13659.
63. Chen F, Haigh S, Barman S, Fulton DJ. From form to function: the role of Nox4 in the cardiovascular system. Front Physiol. 2012;3:412. doi: 10.3389/fphys.2012.00412.
64. Cho KJ, Seo JM, Kim JH. Bioactive lipoxygenase metabolites stimulation of NADPH oxidases and reactive oxygen species. Mol Cells. 2011;32:1-5. doi: 10.1007/s10059-011-1021-7.
65. Goettsch C, Goettsch W, Muller G, Seebach J, Schnittler HJ, Morawietz H. Nox4 overexpression activates reactive oxygen species and p38 MAPK in human endothelial cells. Biochem Biophys Res Commun. 2009;380:355-360. doi: 10.1016/j.bbrc.2009.01.107.
66. Li J, Stouffs M, Serrander L, Banfi B, Bettiol E, Charnay Y, Steger K, Krause KH, Jaconi ME. The NADPH oxidase NOX4 drives cardiac differentiation: role in regulating cardiac transcription factors and MAP kinase activation. Mol Biol Cell. 2006;17:3978-3988. doi: 10.1091/mbc.E05-06-0532.