A proposed mitochondrial-metabolic mechanism for initiation and maintenance of pulmonary arterial hypertension in fawn-hooded rats: The warburg model of pulmonary arterial hypertension

Advances in Experimental Medicine and Biology

Volumn 661, Issue , 2010, Pages 171-185

  Rehman, Jalees ^a   Archer, Stephen L ^a  

^a UNIVERSITY OF CHICAGO   (United States)

Author keywords

Cancer; Epigenetic silencing; Fawn hooded rats (FHR); Glycolysis; Hypoxia inducible factor 1a; Mitochondrial electron transport chain; Pulmonary arterial hypertension (PAH); Pyruvate dehydrogenase kinase; Reactive oxygen species; Vascular smooth muscle cell proliferation Warburg effect

Indexed keywords

HYPOXIA INDUCIBLE FACTOR 1ALPHA; MANGANESE SUPEROXIDE DISMUTASE; PLATELET DERIVED GROWTH FACTOR; PYRUVATE DEHYDROGENASE KINASE; RHO KINASE; TRANSCRIPTION FACTOR NFAT; VOLTAGE GATED POTASSIUM CHANNEL; 5,15 BIS(N (KEMP'S TRIACID IMIDO) 2 TOLYL) 2,8,12,18 TETRAETHYL 3,7,13,17 TETRAMETHYLPORPHYRIN; 5,15-BIS(N-(KEMP'S TRIACID IMIDO)-2-TOLYL)-2,8,12,18-TETRAETHYL-3,7,13,17-TETRAMETHYLPORPHYRIN; HYDROGEN PEROXIDE; OXIDIZING AGENT; PHTHALIMIDE DERIVATIVE; PORPHYRIN; SUPEROXIDE DISMUTASE;

APOPTOSIS; CELL ACTIVITY; CELL FUNCTION; CELL PROLIFERATION; CONFERENCE PAPER; DISEASE ACTIVITY; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DOWN REGULATION; ENZYME ACTIVATION; ENZYME ACTIVITY; EPIGENETICS; EXPERIMENTAL MODEL; FAWN HOODED HYPERTENSIVE RAT; GENE MUTATION; GENE SILENCING; INFLAMMATION; METABOLIC PARAMETERS; MITOCHONDRION; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PULMONARY HYPERTENSION; THROMBOSIS; VASOCONSTRICTION; ANIMAL; DISEASE MODEL; GENETIC EPIGENESIS; GENETICS; HUMAN; METABOLISM; NEOPLASM; RAT; RAT STRAIN; REVIEW;

RATTUS;

ANIMALS; DISEASE MODELS, ANIMAL; EPIGENESIS, GENETIC; GENE SILENCING; HUMANS; HYDROGEN PEROXIDE; HYPERTENSION, PULMONARY; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; MITOCHONDRIA; NEOPLASMS; OXIDANTS; PHTHALIMIDES; PORPHYRINS; RATS; RATS, INBRED STRAINS; SUPEROXIDE DISMUTASE;

EID: 77951220191     PISSN: 00652598     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-1-60761-500-2_11     Document Type: Conference Paper

References (86)

1. Wigley FM, Lima JA, Mayes M, McLain D, Chapin JL, Ward-Able C (2005) The prevalence of undiagnosed pulmonary arterial hypertension in subjects with connective tissue disease at the secondary health care level of community-based rheumatologists (the UNCOVER study). Arthritis Rheum 52:2125-2132 (Pubitemid 40994336)
2. Thenappan T, Shah SJ, Rich S, Gomberg-Maitland M (2007) A USA-based registry for pulmonary arterial hypertension: 1982-2006. Eur Respir J 30:1103-1110 (Pubitemid 351194756)
3. Platoshyn O, Zhang S, McDaniel SS, Yuan JX-J (2002) Cytochrome c activates K+ channels before inducing apoptosis. Am J Physiol Cell Physiol 283:C1298-C1305
4. Pozeg ZI, Michelakis ED, McMurtry MS et al (2003) In vivo gene transfer of the O2-sensitive potassium channel Kv1.5 reduces pulmonary hypertension and restores hypoxic pulmonary vasoconstriction in chronically hypoxic rats. Circulation 107:2037-2044 (Pubitemid 36506080)
5. Remillard CV, Yuan JX-J (2004) Activation of K+ channels: an essential pathway in programmed cell death. Am J Physiol Lung Cell Mol Physiol 286:L49-L67 (Pubitemid 38055858)
6. Merklinger SL, Jones PL, Martinez EC, Rabinovitch M (2005) Epidermal growth factor receptor blockade mediates smooth muscle cell apoptosis and improves survival in rats with pulmonary hypertension. Circulation 112:423-431 (Pubitemid 41022085)
7. Bonnet S, Archer SL, Allalunis-Turner J et al (2007) A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell 11:37-51 (Pubitemid 46054520)
8. Bonnet S, Michelakis ED, Porter CJ et al (2006) An abnormal mitochondrial-HIF-1-Kv channel pathway disrupts oxygen-sensing and triggers pulmonary arterial hypertension (PAH) in fawn-hooded rats: similarities to human PAH. Circulation 113:2630-2641 (Pubitemid 43948012)
9. Yuan JX-J, Aldinger AM, Juhaszova M et al (1998) Dysfunctional voltage-gated K+ channels in pulmonary artery smooth muscle cells of patients with primary pulmonary hypertension. Circulation 98:1400-1406 (Pubitemid 28462800)
10. Archer SL, Gomberg-Maitland M, Maitland ML, Rich S, Garcia JG, Weir EK (2008) Mitochondrial metabolism, redox signaling, and fusion: a mitochondria-ROS-HIF-1(-Kv1.5 O2-sensing pathway at the intersection of pulmonary hypertension and cancer. Am J Physiol Heart Circ Physiol 294:H570-H578 (Pubitemid 351253263)
11. Ishikura K, Yamada N, Ito M et al (2006) Beneficial acute effects of rho-kinase inhibitor in patients with pulmonary arterial hypertension. Circ J 70:174-178 (Pubitemid 43170128)
12. Nagaoka T, Gebb SA, Karoor V et al (2006) Involvement of RhoA/Rho kinase signaling in pulmonary hypertension of the fawn-hooded rat. J Appl Physiol 100:996-1002 (Pubitemid 43671557)
13. Parker TA, Roe G, Grover TR, Abman SH (2006) Rho kinase activation maintains high pulmonary vascular resistance in the ovine fetal lung. Am J Physiol Lung Cell Mol Physiol 291:L976-L982 (Pubitemid 44772060)
14. Xing XQ, Gan Y, Wu SJ, Chen P, Zhou R, Xiang XD (2006) Rho-kinase as a potential therapeutic target for the treatment of pulmonary hypertension. Drug News Perspect 19:517-522 (Pubitemid 46153522)
15. Dorfmuller P, Perros F, Balabanian K, Humbert M (2003) Inflammation in pulmonary arterial hypertension. Eur Respir J 22:358-363 (Pubitemid 36987011)
16. Otterdal K, Andreassen AK, Yndestad A et al (2008) Raised LIGHT levels in pulmonary arterial hypertension: potential role in thrombus formation. Am J Respir Crit Care Med 177:202-207
17. Voelkel NF, Cool C, Lee SD, Wright L, Geraci MW, Tuder RM (1998) Primary pulmonary hypertension between inflammation and cancer. Chest 114:225S-230S (Pubitemid 28435972)
18. Herve P, Launay JM, Scrobohaci ML et al (1995) Increased plasma serotonin in primary pulmonary hypertension. Am J Med 99:249-254
19. Christman BW, McPherson CD, Newman JH et al (1992) An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N Engl J Med 327:70-75
20. Steudel W, Ichinose F, Huang PL et al (1997) Pulmonary vasoconstriction and hypertension in mice with targeted disruption of the endothelial nitric oxide synthase (NOS 3) gene. Circ Res 81:34-41 (Pubitemid 27272980)
21. Stewart DJ, Levy RD, Cernacek P, Langleben D (1991) Increased plasma endothelin-1 in pulmonary hypertension: marker or mediator of disease? Ann Intern Med 114:464-469
22. Sakao S, Taraseviciene-Stewart L, Lee JD, Wood K, Cool CD, Voelkel NF (2005) Initial apoptosis is followed by increased proliferation of apoptosis-resistant endothelial cells. FASEB J 19(9):1178-1180 (Pubitemid 40946457)
23. Cowan KN, Jones PL, Rabinovitch M (2000) Elastase and matrix metalloproteinase inhibitors induce regression, and tenascin-C antisense prevents progression, of vascular disease. J Clin Invest 105:21-34 (Pubitemid 30036384)
24. Krick S, Platoshyn O, Sweeney M, Kim H, Yuan JX-J (2001) Activation of K+ channels induces apoptosis in vascular smooth muscle cells. Am J Physiol Cell Physiol 280:C970-C979
25. Ekhterae D, Platoshyn O, Krick S, Yu Y, McDaniel SS, Yuan JX-J (2001) Bcl-2 decreases voltage-gated K+ channel activity and enhances survival in vascular smooth muscle cells. Am J Physiol Cell Physiol 281:C157-C165
26. Michelakis ED, McMurtry MS, Wu X-C et al (2002) 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 105:244-250 (Pubitemid 34084326)
27. McMurtry MS, Bonnet S, Wu X et al (2004) Dichloroacetate prevents and reverses pulmonary hypertension by inducing pulmonary artery smooth muscle cell apoptosis. Circ Res 95:830-840 (Pubitemid 39390586)
28. McMurtry MS, Archer SL, Altieri DC et al (2005) Gene therapy targeting survivin selectively induces pulmonary vascular apoptosis and reverses pulmonary arterial hypertension. J Clin Invest 115:1479-1491 (Pubitemid 40814657)
29. Morrell NW, Yang X, Upton PD et al (2001) Altered growth responses of pulmonary artery smooth muscle cells from patients with primary pulmonary hypertension to transforming growth factor-b1 and bone morphogenetic proteins. Circulation 104:790-795 (Pubitemid 32762677)
30. McMurtry MS, Moudgil R, Hashimoto K, Bonnet S, Michelakis ED, Archer SL (2007) Overexpression of human bone morphogenetic protein receptor 2 does not ameliorate monocrotaline pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol 292:L872-L878 (Pubitemid 46608233)
31. Eddahibi S, Raffestin B, Hamon M, Adnot S (2002) Is the serotonin transporter involved in the pathogenesis of pulmonary hypertension? J Lab Clin Med 139:194-201 (Pubitemid 34557354)
32. Guignabert C, Izikki M, Tu LI et al (2006) Transgenic mice overexpressing the 5-hydroxytryptamine transporter gene in smooth muscle develop pulmonary hypertension. Circ Res 98:1323-1330 (Pubitemid 43948088)
33. Schermuly RT, Dony E, Ghofrani HA et al (2005) Reversal of experimental pulmonary hypertension by PDGF inhibition. J Clin Invest 115:2811-2821 (Pubitemid 41434408)
34. Archer SL, Souil E, Dinh-Xuan AT et al (1998) Molecular identification of the role of voltagegated K+ channels, Kv1.5 and Kv2.1, in hypoxic pulmonary vasoconstriction and control of resting membrane potential in rat pulmonary artery myocytes. J Clin Invest 101:2319-2330 (Pubitemid 28270426)
35. Archer SL, Wu X-C, Thébaud B et al (2004) Preferential expression and function of voltagegated, O2-sensitive K+ channels in resistance pulmonary arteries explains regional heterogeneity in hypoxic pulmonary vasoconstriction. ionic diversity in smooth muscle cells. Circ Res 95:308-318 (Pubitemid 39056292)
36. Yuan XJ, Wang J, Juhaszova M, Gaine SP, Rubin LJ (1998) Attenuated K+ channel gene transcription in primary pulmonary hypertension. Lancet 351:726-727 (Pubitemid 28105348)
37. Reeve HL, Michelakis E, Nelson DP, Weir EK, Archer SL (2001) Alterations in a redox oxygen sensing mechanism in chronic hypoxia. J Appl Physiol 90:2249-2256 (Pubitemid 32467419)
38. Young KA, Ivester C, West J, Carr M, Rodman DM (2006) BMP signaling controls PASMC KV channel expression in vitro and in vivo. Am J Physiol Lung Cell Mol Physiol 290:L841-L848 (Pubitemid 43725045)
39. Landsberg JW, Yuan JX-J (2004) Calcium and TRP channels in pulmonary vascular smooth muscle cell proliferation. News Physiol Sci 19:44-50
40. Bonnet S, Rochefort G, Sutendra G et al (2007) The nuclear factor of activated T cells in pulmonary arterial hypertension can be therapeutically targeted. Proc Natl Acad Sci USA 104:11418-11423 (Pubitemid 47175155)
41. Davie NJ, Crossno JT, Jr., Frid MG et al (2004) Hypoxia-induced pulmonary artery adventitial remodeling and neovascularization: contribution of progenitor cells. Am J Physiol Lung Cell Mol Physiol 286:L668-L678 (Pubitemid 38365049)
42. Deng Z, Morse JH, Slager SL et al (2000) Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene. Am J Hum Genet 67:737-744 (Pubitemid 30659603)
43. Thomson JR, Machado RD, Pauciulo MW et al (2000) Sporadic primary pulmonary hypertension is associated with germline mutations of the gene encoding BMPR-II, a receptor member of the TGF-b family. J Med Genet 37:741-745
44. West J, Fagan K, Steudel W et al (2004) Pulmonary hypertension in transgenic mice expressing a dominant-negative BMPRII gene in smooth muscle. Circ Res 94:1109-1114 (Pubitemid 38579706)
45. Ricciardi MJ, Knight BP, Martinez FJ, Rubenfire M (1998) Inhaled nitric oxide in primary pulmonary hypertension: a safe and effective agent for predicting response to nifedipine. J Am Coll Cardiol 32:1068-1073 (Pubitemid 28459601)
46. Sitbon O, Humbert M, Jagot JL et al (1998) Inhaled nitric oxide as a screening agent for safely identifying responders to oral calcium-channel blockers in primary pulmonary hypertension. Eur Respir J 12:265-270 (Pubitemid 28389516)
47. West J, Cogan J, Geraci M et al (2008) Gene expression in BMPR2 mutation carriers with and without evidence of pulmonary arterial hypertension suggests pathways relevant to disease penetrance. BMC Med Genomics 1:45
48. Kentera D, Susic D, Veljkovic V, Tucakovic G, Koko V (1988) Pulmonary artery pressure in rats with hereditary platelet function defect. Respiration 54:110-114
49. Cowley AW, Jr., Liang M, Roman RJ, Greene AS, Jacob HJ (2004) Consomic rat model systems for physiological genomics. Acta Physiol Scand 181:585-592 (Pubitemid 39078858)
50. Sato K, Webb S, Tucker A et al (1992) Factors influencing the idiopathic development of pulmonary hypertension in the fawn hooded rat. Am Rev Respir Dis 145:793-797
51. Ashmore RC, Rodman DM, Sato K et al (1991) Paradoxical constriction to platelets by arteries from rats with pulmonary hypertension. Am J Physiol 260:H1929-H1934
52. Bowers R, Cool C, Murphy RC et al (2004) Oxidative stress in severe pulmonary hypertension. Am J Respir Crit Care Med 169:764-769 (Pubitemid 38338929)
53. Tuder RM, Chacon M, Alger L et al (2001) Expression of angiogenesis-related molecules in plexiform lesions in severe pulmonary hypertension: evidence for a process of disordered angiogenesis. J Pathol 195:367-374
54. Burke-Wolin T, Wolin MS (1989) H2O2 and cGMP may function as an O2 sensor in the pulmonary artery. J Appl Physiol 66:167-170 (Pubitemid 19056072)
55. Michelakis ED, Hampl V, Nsair A et al (2002) Diversity in mitochondrial function explains differences in vascular oxygen sensing. Circ Res 90:1307-1315 (Pubitemid 34787413)
56. Wolin MS, Burke TM (1987) Hydrogen peroxide elicits activation of bovine pulmonary arterial soluble guanylate cyclase by a mechanism associated with its metabolism by catalase. Biochem Biophys Res Commun 143:20-25 (Pubitemid 17030458)
57. Michelakis ED, Rebeyka I, Wu X et al (2002) O2 sensing in the human ductus arteriosus: regulation of voltage-gated K+ channels in smooth muscle cells by a mitochondrial redox sensor. Circ Res 91:478-486
58. Guo G, Yan-Sanders Y, Lyn-Cook BD et al (2003) Manganese superoxide dismutasemediated gene expression in radiation-induced adaptive responses. Mol Cell Biol 23:2362-2378 (Pubitemid 36351019)
59. Redout EM, Wagner MJ, Zuidwijk MJ et al (2007) Right-ventricular failure is associated with increased mitochondrial complex II activity and production of reactive oxygen species. Cardiovasc Res 75:770-781 (Pubitemid 47243719)
60. Liu JQ, Zelko IN, Erbynn EM, Sham JSK, Folz RJ (2006) Hypoxic pulmonary hypertension: role of superoxide and NADPH oxidase (gp91phox). Am J Physiol Lung Cell Mol Physiol 290:L2-L10
61. Nozik-Grayck E, Suliman HB, Majka S et al (2008) Lung EC-SOD overexpression attenuates hypoxic induction of Egr-1 and chronic hypoxic pulmonary vascular remodeling. Am J Physiol Lung Cell Mol Physiol 295:L422-L430
62. Li N, Oberley TD, Oberley LW, Zhong W (1998) Overexpression of manganese superoxide dismutase in DU145 human prostate carcinoma cells has multiple effects on cell phenotype. Prostate 35:221-233 (Pubitemid 28211296)
63. Bravard A, Sabatier L, Hoffschir F, Ricoul M, Luccioni C, Dutrillaux B (1992) SOD2: a new type of tumor-suppressor gene? Int J Cancer 51:476-480
64. Hodge DR, Xiao W, Peng B, Cherry JC, Munroe DJ, Farrar WL (2005) Enforced expression of superoxide dismutase 2/manganese superoxide dismutase disrupts autocrine interleukin-6 stimulation in human multiple myeloma cells and enhances dexamethasone-induced apoptosis. Cancer Res 65:6255-6263 (Pubitemid 40994411)
65. Hurt EM, Thomas SB, Peng B, Farrar WL (2007) Molecular consequences of SOD2 expression in epigenetically silenced pancreatic carcinoma cell lines. Br J Cancer 97:1116-1123 (Pubitemid 47587014)
66. Hurt EM, Thomas SB, Peng B, Farrar WL (2007) Integrated molecular profiling of SOD2 expression in multiple myeloma. Blood 109:3953-3962 (Pubitemid 46641748)
67. Hitchler MJ, Oberley LW, Domann FE (2008) Epigenetic silencing of SOD2 by histone modifications in human breast cancer cells. Free Radic Biol Med 45(11):1573-1580
68. Fuks F, Hurd PJ, Deplus R, Kouzarides T (2003) The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase. Nucleic Acids Res 31:2305-2312 (Pubitemid 37442098)
69. Fuks F, Hurd PJ, Wolf D, Nan X, Bird AP, Kouzarides T (2003) The methyl-CpG-binding protein MeCP2 links DNA methylation to histone methylation. J Biol Chem 278:4035-4040 (Pubitemid 36801137)
70. Archer SL, Huang J, Henry T, Peterson D, Weir EK (1993) A redox-based O2 sensor in rat pulmonary vasculature. Circ Res 73:1100-1112 (Pubitemid 23340205)
71. Schroder E, Eaton P (2008) Hydrogen peroxide as an endogenous mediator and exogenous tool in cardiovascular research: issues and considerations. Curr Opin Pharmacol 8:153-159
72. Archer SL, Will JA, Weir EK (1986) Redox status in the control of pulmonary vascular tone. Herz 11:127-141
73. Archer SL, Nelson DP, Weir EK (1989) Simultaneous measurement of O2 radicals and pulmonary vascular reactivity in rat lung. J Appl Physiol 67:1903-1911 (Pubitemid 20039400)
74. Archer SL, Weir EK, Reeve HL, Michelakis E (2000) Molecular identification of O2 sensors and O2-sensitive potassium channels in the pulmonary circulation. Adv Exp Med Biol 475:219-240 (Pubitemid 32197728)
75. Archer SL, Michelakis ED, Thebaudt B et al (2006) A central role for oxygen-sensitive K+ channels and mitochondria in the specialized oxygen-sensing system. Novartis Found Symp 272:157-171; discussion 71-75, 214-217
76. Cadenas E, Davies KJ (2000) Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med 29:222-230
77. Semenza GL (2004) O2-regulated gene expression: transcriptional control of cardiorespiratory physiology by HIF-1. J Appl Physiol 96:1173-1177; discussion 0-2 (Pubitemid 38248698)
78. Kim JW, Tchernyshyov I, Semenza GL, Dang CV (2006) HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metab 3:177-185
79. Shimoda LA, Manalo DJ, Sham JSK, Semenza GL, Sylvester JT (2001) Partial HIF-1a deficiency impairs pulmonary arterial myocyte electrophysiological responses to hypoxia. Am J Physiol Lung Cell Mol Physiol 281:L202-L208
80. Huang LE, Arany Z, Livingston DM, Bunn HF (1996) Activation of hypoxia-inducible transcription factor depends primarily upon redox-sensitive stabilization of its alpha subunit. J Biol Chem 271:32253-32259 (Pubitemid 26422262)
81. Wang GL, Jiang BH, Semenza GL (1995) Effect of altered redox states on expression and DNA-binding activity of hypoxia-inducible factor 1. Biochem Biophys Res Commun 212:550-556
82. Roche TE, Baker JC, Yan X et al (2001) Distinct regulatory properties of pyruvate dehydrogenase kinase and phosphatase isoforms. Prog Nucleic Acid Res Mol Biol 70:33-75
83. Mayers RM, Leighton B, Kilgour E (2005) PDH kinase inhibitors: a novel therapy for Type II diabetes? Biochem Soc Trans 33:367-370 (Pubitemid 40604374)
84. Freeman BA, Crapo JD (1981) Hyperoxia increases oxygen radical production in rat lungs and lung mitochondria. J Biol Chem 256:10986-10992 (Pubitemid 12181585)
85. Morrell JA, Orme J, Butlin RJ, Roche TE, Mayers RM, Kilgour E (2003) AZD7545 is a selective inhibitor of pyruvate dehydrogenase kinase 2. Biochem Soc Trans 31:1168-1170 (Pubitemid 38030932)
86. Silverman LR, Mufti GJ (2005) Methylation inhibitor therapy in the treatment of myelodysplastic syndrome. Nat Clin Pract Oncol 2(Suppl 1):S12-S23 (Pubitemid 43135230)