Role of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid in hypoxia-induced pulmonary hypertension

Journal of Physiological Sciences

Volumn 62, Issue 3, 2012, Pages 163-172

  Zhu, Daling ^a,b   Ran, Yajuan ^b  

^a HARBIN MEDICAL UNIVERSITY   (China)

^b Biopharmaceutical Key Laboratory of Heilongjiang Province   (China)

Author keywords

15 Hydroxyeicosatetraenoic acid; 15 Lipoxygenase; Hypoxic pulmonary hypertension; Remodeling; Vasoconstriction

Indexed keywords

15 HYDROXY 5,8,11,13 ICOSATETRAENOIC ACID; 15-HYDROXY-5,8,11,13-EICOSATETRAENOIC ACID; ARACHIDONATE 15 LIPOXYGENASE; ARACHIDONIC ACID; HYDROXYICOSATETRAENOIC ACID;

ANIMAL; ANOXIA; APOPTOSIS; DRUG EFFECT; HUMAN; METABOLISM; PATHOPHYSIOLOGY; PHYSIOLOGY; PULMONARY HYPERTENSION; REVIEW; VASCULAR SMOOTH MUSCLE; VASOCONSTRICTION;

ANIMALS; ANOXIA; APOPTOSIS; ARACHIDONATE 15-LIPOXYGENASE; ARACHIDONIC ACID; HUMANS; HYDROXYEICOSATETRAENOIC ACIDS; HYPERTENSION, PULMONARY; MUSCLE, SMOOTH, VASCULAR; VASOCONSTRICTION;

EID: 84860716076     PISSN: 18806546     EISSN: None     Source Type: Journal    
DOI: 10.1007/s12576-012-0196-9     Document Type: Review

References (101)

1. Rabinovitch M (2008) Molecular pathogenesis of pulmonary arterial hypertension. J Clin Invest 118 (7): 2372-2379 (Pubitemid 351949764)
2. Stenmark KR, Fagan KA, Frid MG (2006) Hypoxia-induced pulmonary vascular remodeling: cellular and molecular mechanisms. Circ Res 99 (7): 675-691 (Pubitemid 44498302)
3. Mauban JR, Remillard CV, Yuan JX (2005) Hypoxic pulmonary vasoconstriction: role of ion channels. J Appl Physiol 98 (1): 415-420 (Pubitemid 40041275)
4. Mandegar M, Fung YC, Huang W, Remillard CV, Rubin LJ, Yuan JX (2004) Cellular and molecular mechanisms of pulmonary vascular remodeling: role in the development of pulmonary hypertension. Microvasc Res 68 (2): 75-103 (Pubitemid 39093882)
5. Gurbanov E, Shiliang X (2006) The key role of apoptosis in the pathogenesis and treatment of pulmonary hypertension. Eur J Cardiothorac Surg 30 (3): 499-507 (Pubitemid 44189855)
6. Radmark O (2002) Arachidonate 5-lipoxygenase. Prostaglandins Other Lipid Mediat 68-69: 211-234
7. Jisaka M, Kim RB, Boeglin WE, Nanney LB, Brash AR (1997) Molecular cloning and functional expression of a phorbol esterinducible 8S-lipoxygenase from mouse skin. J Biol Chem 272 (39): 24410-24416 (Pubitemid 27418648)
8. Krieg P, Kinzig A, Heidt M, Marks F, Furstenberger G (1998) cDNA cloning of a 8-lipoxygenase and a novel epidermis-type lipoxygenase from phorbol ester-treated mouse skin. Biochim Biophys Acta 1391 (1): 7-12 (Pubitemid 28143970)
9. Yoshimoto T, Takahashi Y (2002) Arachidonate 12-lipoxygenases. Prostaglandins Other Lipid Mediat 68-69: 245-262
10. Kuhn H, Walther M, Kuban RJ (2002) Mammalian arachidonate 15-lipoxygenases structure, function, and biological implications. Prostaglandins Other Lipid Mediat 68-69: 263-290
11. Cuzzocrea S, Rossi A, Mazzon E, Di Paola R, Genovese T, Muia C, Caputi AP, Sautebin L (2005) 5-Lipoxygenase modulates colitis through the regulation of adhesion molecule expression and neutrophil migration. Lab Invest 85 (6): 808-822 (Pubitemid 40799710)
12. Wen Y, Gu J, Chakrabarti SK, Aylor K, Marshall J, Takahashi Y, Yoshimoto T, Nadler JL (2007) The role of 12/15-lipoxygenase in the expression of interleukin-6 and tumor necrosis factor-alpha in macrophages. Endocrinology 148 (3): 1313-1322
13. Huber J, Furnkranz A, Bochkov VN, Patricia MK, Lee H, Hedrick CC, Berliner JA, Binder BR, Leitinger N (2006) Specific monocyte adhesion to endothelial cells induced by oxidized phospholipids involves activation of cPLA2 and lipoxygenase. J Lipid Res 47 (5): 1054-1062 (Pubitemid 43764701)
14. Dronadula N, Rizvi F, Blaskova E, Li Q, Rao GN (2006) Involvement of cAMP-response element binding protein-1 in arachidonic acid-induced vascular smooth muscle cell motility. J Lipid Res 47 (4): 767-777
15. Sigal E, Grunberger D, Craik CS, Caughey GH, Nadel JA (1988) Arachidonate 15-lipoxygenase (omega-6 lipoxygenase) from human leukocytes. Purification and structural homology to other mammalian lipoxygenases. J Biol Chem 263 (11): 5328-5332
16. Brash AR, Boeglin WE, Chang MS (1997) Discovery of a second 15S-lipoxygenase in humans. Proc Natl Acad Sci USA 94 (12): 6148-6152 (Pubitemid 27270652)
17. Schewe T, Halangk W, Hiebsch C, Rapoport SM (1975) A lipoxygenase in rabbit reticulocytes which attacks phospholipids and intact mitochondria. FEBS Lett 60 (1): 149-152
18. Gillmor SA, Villasenor A, Fletterick R, Sigal E, Browner MF (1997) The structure of mammalian 15-lipoxygenase reveals similarity to the lipases and the determinants of substrate specificity. Nat Struct Biol 4 (12): 1003-1009 (Pubitemid 27525804)
19. Ivanov I, Schwarz K, Holzhutter HG, Myagkova G, Kuhn H (1998) Omega-oxidation impairs oxidizability of polyenoic fatty acids by 15-lipoxygenases: consequences for substrate orientation at the active site. Biochem J 336 (Pt 2): 345-352 (Pubitemid 28564390)
20. Salzmann-Reinhardt U, Kuhn H, Wiesner R, Rapoport S (1985) Metabolism of polyunsaturated fatty acids by rabbit reticulocytes. Eur J Biochem 153 (1): 189-194 (Pubitemid 16191286)
21. Goetzl EJ, An S, Smith WL (1995) Specificity of expression and effects of eicosanoid mediators in normal physiology and human diseases. FASEB J 9 (11): 1051-1058
22. Samuelsson B, Dahlen SE, Lindgren JA, Rouzer CA, Serhan CN (1987) Leukotrienes and lipoxins: structures, biosynthesis, and biological effects. Science 237 (4819): 1171-1176 (Pubitemid 17131222)
23. Yamada M, Proia AD (2000) 8 (S)-hydroxyeicosatetraenoic acid is the lipoxygenase metabolite of arachidonic acid that regulates epithelial cell migration in the rat cornea. Cornea 19 (3 Suppl): S13-S20 (Pubitemid 30327280)
24. Gschwendt M, Furstenberger G, Kittstein W, Besemfelder E, Hull WE, Hagedorn H, Opferkuch HJ, Marks F (1986) Generation of the arachidonic acid metabolite 8-HETE by extracts of mouse skin treated with phorbol ester in vivo; identification by 1H-n.m.r. and GC-MS spectroscopy. Carcinogenesis 7 (3): 449-455 (Pubitemid 17135324)
25. Pace-Asciak CR, Granstrom E, Samuelsson B (1983) Arachidonic acid epoxides. Isolation and structure of two hydroxyl epoxide intermediates in the formation of 8,11,12-and 10,11,12-trihydroxyeicosatrienoic acids. J Biol Chem 258 (11): 6835-6840
26. Brash AR (1999) Lipoxygenases: occurrence, functions, catalysis, and acquisition of substrate. J Biol Chem 274 (34): 23679-23682
27. Kuhn H, Thiele BJ (1999) The diversity of the lipoxygenase family. Many sequence data but little information on biological significance. FEBS Lett 449 (1): 7-11 (Pubitemid 29182660)
28. Gray PR, Derksen FJ, Broadstone RV, Robinson NE, Johnson HG, Olson NC (1992) Increased pulmonary production of immunoreactive 15- hydroxyeicosatetraenoic acid in an animal model of asthma. Am Rev Respir Dis 145 (5): 1092-1097
29. Profita M, Sala A, Riccobono L, Paterno A, Mirabella A, Bonanno A, Guerrera D, Pace E, Bonsignore G, Bousquet J, Vignola AM (2000) 15-Lipoxygenase expression and 15 (S)-hydroxyeicoisatetraenoic acid release and reincorporation in induced sputum of asthmatic subjects. J Allergy Clin Immunol 105 (4): 711-716 (Pubitemid 30226444)
30. Profita M, Sala A, Riccobono L, Pace E, Paterno A, Zarini S, Siena L, Mirabella A, Bonsignore G, Vignola AM (2000) 15 (S)-HETE modulates LTB (4) production and neutrophil chemotaxis in chronic bronchitis. Am J Physiol Cell Physiol 279 (4): C1249-C1258
31. Donowitz M (1985) Arachidonic acid metabolites and their role in inflammatory bowel disease. An update requiring addition of a pathway. Gastroenterology 88 (2): 580-587 (Pubitemid 15194728)
32. Vanderhoek JY, Bryant RW, Bailey JM (1980) Inhibition of leukotriene biosynthesis by the leukocyte product 15-hydroxy-5,8,11,13-eicosatetraenoic acid. J Biol Chem 255 (21): 10064-10066
33. Petrich K, Ludwig P, Kuhn H, Schewe T (1996) The suppression of 5-lipoxygenation of arachidonic acid in human polymorphonuclear leucocytes by the 15-lipoxygenase product (15S)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoic acid: structureactivity relationship and mechanism of action. Biochem J 314 (Pt 3): 911-916
34. Vachier I, Chanez P, Bonnans C, Godard P, Bousquet J, Chavis C (2002) Endogenous anti-inflammatory mediators from arachidonate in human neutrophils. Biochem Biophys Res Commun 290 (1): 219-224 (Pubitemid 34694486)
35. Profita M, Sala A, Siena L, Henson PM, Murphy RC, Paterno A, Bonanno A, Riccobono L, Mirabella A, Bonsignore G, Vignola AM (2002) Leukotriene B4 production in human mononuclear phagocytes is modulated by interleukin-4-induced 15-lipoxygenase. J Pharmacol Exp Ther 300 (3): 868-875 (Pubitemid 34164990)
36. Takata S, Papayianni A, Matsubara M, Jimenez W, Pronovost PH, Brady HR (1994) 15-Hydroxyeicosatetraenoic acid inhibits neutrophil migration across cytokine-activated endothelium. Am J Pathol 145 (3): 541-549
37. Munger KA, Montero A, Fukunaga M, Uda S, Yura T, Imai E, Kaneda Y, Valdivielso JM, Badr KF (1999) Transfection of rat kidney with human 15-lipoxygenase suppresses inflammation and preserves function in experimental glomerulonephritis. Proc Natl Acad Sci USA 96 (23): 13375-13380
38. Holtzman MJ, Zhang V, Hussain H, Roswit WT, Wilson JD (1994) Prostaglandin H synthase and lipoxygenase gene families in the epithelial cell barrier. Ann N Y Acad Sci 744: 58-77 (Pubitemid 26005811)
39. Schewe T, Rapoport SM, Kuhn H (1986) Enzymology and physiology of reticulocyte lipoxygenase: comparison with other lipoxygenases. Adv Enzymol Relat Areas Mol Biol 58: 191-272
40. Rapoport SM, Schewe T, Thiele B, Dubiel W (1982) The role of lipoxygenase and ATP-dependent proteolysis in the maturation of the reticulocyte. Prog Clin Biol Res 102 (pt A): 47-58
41. Grullich C, Duvoisin RM, Wiedmann M, van Leyen K (2001) Inhibition of 15-lipoxygenase leads to delayed organelle degradation in the reticulocyte. FEBS Lett 489 (1): 51-54 (Pubitemid 32176004)
42. Postoak D, Nystuen L, King L, Ueno M, Beckman BS (1990) 15-Lipoxygenase products of arachidonate play a role in proliferation of transformed erythroid cells. Am J Physiol 259 (6 Pt 1): C849-C853
43. Palmberg L, Lindgren JA, Thyberg J, Claesson HE (1991) On the mechanism of induction of DNA synthesis in cultured arterial smooth muscle cells by leukotrienes. Possible role of prostaglandin endoperoxide synthase products and plateletderived growth factor. J Cell Sci 98 (Pt 2): 141-149 (Pubitemid 21924962)
44. Ma C, Li Y, Ma J, Liu Y, Li Q, Niu S, Shen Z, Zhang L, Pan Z, Zhu D (2011) Key role of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid in pulmonary vascular remodeling and vascular angiogenesis associated with hypoxic pulmonary hypertension. Hypertension 58: 679-688
45. Miller YI, Chang MK, Funk CD, Feramisco JR, Witztum JL (2001) 12/15-lipoxygenase translocation enhances site-specific actin polymerization in macrophages phagocytosing apoptotic cells. J Biol Chem 276 (22): 19431-19439
46. Ikawa H, Kamitani H, Calvo BF, Foley JF, Eling TE (1999) Expression of 15-lipoxygenase-1 in human colorectal cancer. Cancer Res 59 (2): 360-366 (Pubitemid 29048868)
47. Moody TW, Leyton J, Martinez A, Hong S, Malkinson A, Mulshine JL (1998) Lipoxygenase inhibitors prevent lung carcinogenesis and inhibit non-small cell lung cancer growth. Exp Lung Res 24 (4): 617-628 (Pubitemid 28308955)
48. Shureiqi I, Chen D, Lotan R, Yang P, Newman RA, Fischer SM, Lippman SM (2000) 15-Lipoxygenase-1 mediates nonsteroidal anti-inflammatory drug-induced apoptosis independently of cyclooxygenase-2 in colon cancer cells. Cancer Res 60 (24): 6846-6850 (Pubitemid 32059150)
49. Mahipal SV, Subhashini J, Reddy MC, Reddy MM, Anilkumar K, Roy KR, Reddy GV, Reddanna P (2007) Effect of 15-lipoxygenase metabolites, 15-(S)-HPETE and 15-(S)-HETE on chronic myelogenous leukemia cell line K-562: reactive oxygen species (ROS) mediate caspase-dependent apoptosis. Biochem Pharmacol 74 (2): 202-214 (Pubitemid 46890813)
50. Wittwer J, Hersberger M (2007) The two faces of the 15-lipoxygenase in atherosclerosis. Prostaglandins Leukot Essent Fatty Acids 77 (2): 67-77 (Pubitemid 47539103)
51. Harats D, Shaish A, George J, Mulkins M, Kurihara H, Levkovitz H, Sigal E (2000) Overexpression of 15-lipoxygenase in vascular endothelium accelerates early atherosclerosis in LDL receptor-deficient mice. Arterioscler Thromb Vasc Biol 20 (9): 2100-2105
52. Shen J, Herderick E, Cornhill JF, Zsigmond E, Kim HS, Kuhn H, Guevara NV, Chan L (1996) Macrophage-mediated 15-lipoxygenase expression protects against atherosclerosis development. J Clin Invest 98 (10): 2201-2208 (Pubitemid 26394192)
53. Zhu D, Medhora M, Campbell WB, Spitzbarth N, Baker JE, Jacobs ER (2003) Chronic hypoxia activates lung 15-lipoxygenase, which catalyzes production of 15-HETE and enhances constriction in neonatal rabbit pulmonary arteries. Circ Res 92 (9): 992-1000 (Pubitemid 36588498)
54. Ma J, Liang S, Wang Z, Zhang L, Jiang J, Zheng J, Yu L, Zheng X, Wang R, Zhu D (2010) ROCK pathway participates in the processes that 15-hydroxyeicosatetraenoic acid (15-HETE) mediated the pulmonary vascular remodeling induced by hypoxia in rat. J Cell Physiol 222 (1): 82-94
55. Zheng X, Li Q, Tang X, Liang S, Chen L, Zhang S, Wang Z, Guo L, Zhang R, Zhu D (2008) Source of the elevation Ca2+ evoked by 15-HETE in pulmonary arterial myocytes. Eur J Pharmacol 601 (1-3): 16-22
56. Ward JP, Robertson TP, Aaronson PI (2005) Capacitative calcium entry: a central role in hypoxic pulmonary vasoconstriction? Am J Physiol Lung Cell Mol Physiol 289 (1): L2-L4 (Pubitemid 40863548)
57. Li S, Ran Y, Zheng X, Pang X, Wang Z, Zhang R, Zhu D (2010) 15-HETE mediates sub-acute hypoxia-induced TRPC1 expression and enhanced capacitative calcium entry in rat distal pulmonary arterial myocytes. Prostaglandins Other Lipid Mediat 93 (1-2): 60-74
58. Verin AD, Cooke C, Herenyiova M, Patterson CE, Garcia JG (1998) Role of Ca2+/calmodulin-dependent phosphatase 2B in thrombin-induced endothelial cell contractile responses. Am J Physiol 275 (4 Pt 1): L788-L799
59. Post JM, Hume JR, Archer SL, Weir EK (1992) Direct role for potassium channel inhibition in hypoxic pulmonary vasoconstriction. Am J Physiol 262 (4 Pt 1): C882-C890
60. Weir EK, Archer SL (1995) The mechanism of acute hypoxic pulmonary vasoconstriction: the tale of two channels. FASEB J 9 (2): 183-189
61. Yuan XJ (1995) Voltage-gated K+ currents regulate resting membrane potential and [Ca2+]i in pulmonary arterial myocytes. Circ Res 77 (2): 370-378
62. Post JM, Gelband CH, Hume JR (1995) [Ca2+]i inhibition of K+ channels in canine pulmonary artery. Novel mechanism for hypoxia-induced membrane depolarization. Circ Res 77 (1): 131-139
63. Archer SL, Huang JM, Reeve HL, Hampl V, Tolarova S, Michelakis E, Weir EK (1996) Differential distribution of electrophysiologically distinct myocytes in conduit and resistance arteries determines their response to nitric oxide and hypoxia. Circ Res 78 (3): 431-442 (Pubitemid 26068959)
64. Han WN, Li XH, Jiang ZY, Ji HY, Huang LJ, Wang ZM, Zhu DL (2004) Effect of 15-HETE on potassium channels of rabbit pulmonary arterial smooth muscles during hypoxia. Sheng Li Xue Bao 56 (6): 717-722
65. Guo L, Tang X, Tian H, Liu Y, Wang Z, Wu H, Wang J, Guo S, Zhu D (2008) Subacute hypoxia suppresses Kv3.4 channel expression and whole-cell K+ currents through endogenous 15-hydroxyeicosatetraenoic acid in pulmonary arterial smooth muscle cells. Eur J Pharmacol 587 (1-3): 187-195
66. Chu X, Tang X, Guo L, Bao H, Zhang S, Zhang J, Zhu D (2009) Hypoxia suppresses KV1.5 channel expression through endogenous 15-HETE in rat pulmonary artery. Prostaglandins Other Lipid Mediat 88 (1-2): 42-50
67. Guo L, Qiu Z, Zhang L, Chen S, Zhu D (2010) Hypoxia suppresses Kv 2.1 channel expression through endogenous 15-hydroxyeicosatetraenoic acid in rat pulmonary artery. J Physiol Sci 60 (5): 373-381
68. Fike CD, Kaplowitz MR, Thomas CJ, Nelin LD (1998) Chronic hypoxia decreases nitric oxide production and endothelial nitric oxide synthase in newborn pig lungs. Am J Physiol 274 (4 Pt 1): L517-L526
69. Guo L, Tang X, Chu X, Sun L, Zhang L, Qiu Z, Chen S, Li Y, Zheng X, Zhu D (2009) Role of protein kinase C in 15-HETEinduced hypoxic pulmonary vasoconstriction. Prostaglandins Leukot Essent Fatty Acids 80 (2-3): 115-123
70. Ye H, Bi HR, Lu CL, Tang XB, Zhu DL (2005) 15-hydroxyeicosatetraenoic acid depressed endothelial nitric oxide synthase activity in pulmonary artery. Sheng Li Xue Bao 57 (5): 612-618
71. Li X, Ma C, Zhu D, Meng L, Guo L, Wang Y, Zhang L, Li Z, Li E (2010) Increased expression and altered subcellular distribution of PKC-delta and PKC-varepsilon in pulmonary arteries exposed to hypoxia and 15-HETE. Prostaglandins Other Lipid Mediat 93 (3-4): 84-92
72. Wang Y, Liang D, Wang S, Qiu Z, Chu X, Chen S, Li L, Nie X, Zhang R, Wang Z, Zhu D (2010) Role of the G-protein and tyrosine kinase-Rho/ROK pathways in 15-hydroxyeicosatetraenoic acid induced pulmonary vasoconstriction in hypoxic rats. J Biochem 147 (5): 751-764
73. Lu C, Liu Y, Tang X, Ye H, Zhu D (2006) Role of 15- hydroxyeicosatetraenoic acid in phosphorylation of ERK1/2 and caldesmon in pulmonary arterial smooth muscle cells. Can J Physiol Pharmacol 84 (10): 1061-1069
74. Rabinovitch M, Gamble W, Nadas AS, Miettinen OS, Reid L (1979) Rat pulmonary circulation after chronic hypoxia: hemodynamic and structural features. Am J Physiol 236 (6): H818-H827 (Pubitemid 9220431)
75. Durmowicz AG, Stenmark KR (1999) Mechanisms of structural remodeling in chronic pulmonary hypertension. Pediatr Rev 20 (11): e91-e102
76. Yu WC, Guo CH (2007) Apoptosis versus proliferation activities of pulmonary artery smooth muscle cells in pulmonary arterial hypertension associated with chronic obstructive pulmonary disease. Zhonghua Jie He He Hu Xi Za Zhi 30 (9): 657-661
77. Wang S, Wang Y, Jiang J, Wang R, Li L, Qiu Z, Wu H, Zhu D (2010) 15-HETE protects rat pulmonary arterial smooth muscle cells from apoptosis via the PI3K/Akt pathway. Prostaglandins Other Lipid Mediat 91 (1-2): 51-60
78. Zhang L, Ma J, Li Y, Guo L, Ran Y, Liu S, Jiang C, Zhu D (2010) 15-Hydroxyeicosatetraenoic acid (15-HETE) protects pulmonary artery smooth muscle cells against apoptosis via HSP90. Life Sci 87 (7-8): 223-231
79. Jiang J, Wang S, Wang Z, Ma J, Liu S, Li W, Zhu D (2011) The role of ERK1/2 in 15-HETE-inhibited apoptosis in pulmonary arterial smooth muscle cells. J Recept Signal Transduct Res 31 (1): 45-52
80. Nie X, Song S, Zhang L, Qiu Z, Shi S, Liu Y, Yao L, Zhu D (2012) 15-Hydroxyeicosatetraenoic acid (15-HETE) protects pulmonary artery smooth muscle cells from apoptosis via inducible nitric oxide synthase (iNOS) pathway. Prostaglandins Other Lipid Mediat 97: 50-59
81. Platoshyn O, Golovina VA, Bailey CL, Limsuwan A, Krick S, Juhaszova M, Seiden JE, Rubin LJ, Yuan JX (2000) Sustained membrane depolarization and pulmonary artery smooth muscle cell proliferation. Am J Physiol Cell Physiol 279 (5): C1540-C1549
82. Burg ED, Remillard CV, Yuan JX (2008) Potassium channels in the regulation of pulmonary artery smooth muscle cell proliferation and apoptosis: pharmacotherapeutic implications. Br J Pharmacol 153 (Suppl 1): S99-S111 (Pubitemid 351341007)
83. Li Y, Li Q, Wang Z, Liang D, Liang S, Tang X, Guo L, Zhang R, Zhu D (2009) 15-HETE suppresses K (+) channel activity and inhibits apoptosis in pulmonary artery smooth muscle cells. Apoptosis 14 (1): 42-51
84. Hislop A, Reid L (1976) New findings in pulmonary arteries of rats with hypoxia-induced pulmonary hypertension. Br J Exp Pathol 57 (5): 542-554
85. Partovian C, Adnot S, Raffestin B, Louzier V, Levame M, Mavier IM, Lemarchand P, Eddahibi S (2000) Adenovirusmediated lung vascular endothelial growth factor overexpression protects against hypoxic pulmonary hypertension in rats. Am J Respir Cell Mol Biol 23 (6): 762-771 (Pubitemid 32013268)
86. Howell K, Preston RJ, McLoughlin P (2003) Chronic hypoxia causes angiogenesis in addition to remodelling in the adult rat pulmonary circulation. J Physiol 547 (Pt 1): 133-145 (Pubitemid 36285169)
87. Christou H, Yoshida A, Arthur V, Morita T, Kourembanas S (1998) 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 (Pubitemid 128358423)
88. Sands M, Howell K, Costello CM, McLoughlin P (2011) Placenta growth factor and vascular endothelial growth factor B expression in the hypoxic lung. Respir Res 12: 17
89. Hyvelin JM, Howell K, Nichol A, Costello CM, Preston RJ, McLoughlin P (2005) Inhibition of Rho-kinase attenuates hypoxia-induced angiogenesis in the pulmonary circulation. Circ Res 97 (2): 185-191 (Pubitemid 41033475)
90. Wright L, Tuder RM, Wang J, Cool CD, Lepley RA, Voelkel NF (1998) 5-Lipoxygenase and 5-lipoxygenase activating protein (FLAP) immunoreactivity in lungs from patients with primary pulmonary hypertension. Am J Respir Crit Care Med 157 (1): 219-229 (Pubitemid 28071286)
91. Voelkel NF, Tuder RM, Wade K, Hoper M, Lepley RA, Goulet JL, Koller BH, Fitzpatrick F (1996) Inhibition of 5-lipoxygenase-activating protein (FLAP) reduces pulmonary vascular reactivity and pulmonary hypertension in hypoxic rats. J Clin Invest 97 (11): 2491-2498
92. Chu SJ, Tang LO, Watney E, Chi EY, Henderson WR Jr (2000) In situ amplification of 5-lipoxygenase and 5-lipoxygenaseactivating protein in allergic airway inflammation and inhibition by leukotriene blockade. J Immunol 165 (8): 4640-4648
93. Stenmark KR, James SL, Voelkel NF, Toews WH, Reeves JT, Murphy RC (1983) Leukotriene C4 and D4 in neonates with hypoxemia and pulmonary hypertension. N Engl J Med 309 (2): 77-80 (Pubitemid 13063590)
94. Piperno D, Pacheco Y, Hosni R, Moliere P, Gharib C, Lagarde M, Perrin-Fayolle M (1993) Increased plasma levels of atrial natriuretic factor, renin activity, and leukotriene C4 in chronic obstructive pulmonary disease. Chest 104 (2): 454-459 (Pubitemid 23229515)
95. Walker JL, Loscalzo J, Zhang YY (2002) 5-Lipoxygenase and human pulmonary artery endothelial cell proliferation. Am J Physiol Heart Circ Physiol 282 (2): H585-H593 (Pubitemid 34654982)
96. Morganroth ML, Stenmark KR, Zirrolli JA, Mauldin R, Mathias M, Reeves JT, Murphy RC, Voelkel NF (1984) Leukotriene C4 production during hypoxic pulmonary vasoconstriction in isolated rat lungs. Prostaglandins 28 (6): 867-875 (Pubitemid 15179710)
97. Morganroth ML, Stenmark KR, Morris KG, Murphy RC, Mathias M, Reeves JT, Voelkel NF (1985) Diethylcarbamazine inhibits acute and chronic hypoxic pulmonary hypertension in awake rats. Am Rev Respir Dis 131 (4): 488-492 (Pubitemid 15086728)
98. Jones JE, Walker JL, Song Y, Weiss N, Cardoso WV, Tuder RM, Loscalzo J, Zhang YY (2004) Effect of 5-lipoxygenase on the development of pulmonary hypertension in rats. Am J Physiol Heart Circ Physiol 286 (5): H1775-H1784 (Pubitemid 38525466)
99. Song Y, Jones JE, Beppu H, Keaney JF Jr, Loscalzo J, Zhang YY (2005) Increased susceptibility to pulmonary hypertension in heterozygous BMPR2-mutant mice. Circulation 112 (4): 553-562 (Pubitemid 41060796)
100. Song Y, Coleman L, Shi J, Beppu H, Sato K, Walsh K, Loscalzo J, Zhang YY (2008) Inflammation, endothelial injury, and persistent pulmonary hypertension in heterozygous BMPR2-mutant mice. Am J Physiol Heart Circ Physiol 295 (2): H677-H690
101. Preston IR, Hill NS, Warburton RR, Fanburg BL (2006) Role of 12-lipoxygenase in hypoxia-induced rat pulmonary artery smooth muscle cell proliferation. Am J Physiol Lung Cell Mol Physiol 290 (2): L367-L374