A metabolic remodeling in right ventricular hypertrophy is associated with decreased angiogenesis and a transition from a compensated to a decompensated state in pulmonary hypertension

Journal of Molecular Medicine

Volumn 91, Issue 11, 2013, Pages 1315-1327

  Sutendra, Gopinath ^a   Dromparis, Peter ^a   Paulin, Roxane ^a   Zervopoulos, Sotirios ^a   Haromy, Alois ^a   Nagendran, Jayan ^a   Michelakis, Evangelos D ^a  

^a UNIVERSITY OF ALBERTA   (Canada)

Author keywords

Angiogenesis; Hypoxia inducible factor 1 ; Ischemia; Metabolism; Right ventricular failure

Indexed keywords

GLUCOSE TRANSPORTER 1; HYPOXIA INDUCIBLE FACTOR 1ALPHA; LECTIN; MONOCROTALINE; PROTEIN P53; PYRUVATE DEHYDROGENASE KINASE; REACTIVE OXYGEN METABOLITE; STROMAL CELL DERIVED FACTOR 1; VASCULOTROPIN;

ANGIOGENESIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASCITES; COMPUTER ASSISTED EMISSION TOMOGRAPHY; CONTROLLED STUDY; DISEASE COURSE; DOWN REGULATION; GLUCOSE TRANSPORT; HEART OUTPUT; HEART RIGHT VENTRICLE FAILURE; HEART RIGHT VENTRICLE HYPERTROPHY; IN VIVO STUDY; MALE; MITOCHONDRION; NONHUMAN; PULMONARY HYPERTENSION; RAT; RAT MODEL; SYSTOLIC BLOOD PRESSURE; WEIGHT REDUCTION;

ANIMALS; GLUCOSE; GLUCOSE TRANSPORTER TYPE 1; HEART VENTRICLES; HYPERTENSION, PULMONARY; HYPERTROPHY, RIGHT VENTRICULAR; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; MALE; MITOCHONDRIA; NEOVASCULARIZATION, PATHOLOGIC; RATS; RATS, SPRAGUE-DAWLEY; REACTIVE OXYGEN SPECIES;

EID: 84888636768     PISSN: 09462716     EISSN: 14321440     Source Type: Journal    
DOI: 10.1007/s00109-013-1059-4     Document Type: Article

References (48)

1. Bogaard HJ, Abe K, Vonk Noordegraaf A, Voelkel NF (2009) The right ventricle under pressure: cellular and molecular mechanisms of right-heart failure in pulmonary hypertension. Chest 135:794-804
2. Haddad F, Ashley E, Michelakis ED (2010) New insights for the diagnosis and management of right ventricular failure, from molecular imaging to targeted right ventricular therapy. Curr Opin Cardiol 25:131-140
3. Haddad F, Hunt SA, Rosenthal DN, Murphy DJ (2008) Right ventricular function in cardiovascular disease, part I: anatomy, physiology, aging, and functional assessment of the right ventricle. Circulation 117:1436-1448
4. Haddad F, Doyle R, Murphy DJ, Hunt SA (2008) Right ventricular function in cardiovascular disease, part II: pathophysiology, clinical importance, and management of right ventricular failure. Circulation 117:1717-1731
5. McLaughlin VV, Presberg KW, Doyle RL, Abman SH, McCrory DC, Fortin T, Ahearn G (2004) Prognosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest 126:78S-92S
6. Bogaard HJ, Natarajan R, Henderson SC, Long CS, Kraskauskas D, Smithson L, Ockaili R, McCord JM, Voelkel NF (2009) Chronic pulmonary artery pressure elevation is insufficient to explain right heart failure. Circulation 120:1951-1960
7. van de Veerdonk MC, Kind T, Marcus JT, Mauritz GJ, Heymans MW, Bogaard HJ, Boonstra A, Marques KM, Westerhof N, Vonk-Noordegraaf A (2011) Progressive right ventricular dysfunction in patients with pulmonary arterial hypertension responding to therapy. J Am Coll Cardiol 58:2511-2519
8. Srivastava D (2006) Making or breaking the heart: from lineage determination to morphogenesis. Cell 126:1037-1048
9. Bishop SP, Altschuld RA (1970) Increased glycolytic metabolism in cardiac hypertrophy and congestive failure. Am J Physiol 218:153-159
10. Piao L, Fang YH, Cadete VJ, Wietholt C, Urboniene D, Toth PT, Marsboom G, Zhang HJ, Haber I, Rehman J et al (2010) The inhibition of pyruvate dehydrogenase kinase improves impaired cardiac function and electrical remodeling in two models of right ventricular hypertrophy: resuscitating the hibernating right ventricle. J Mol Med 88:47-60
11. Gomez A, Bialostozky D, Zajarias A, Santos E, Palomar A, Martinez ML, Sandoval J (2001) Right ventricular ischemia in patients with primary pulmonary hypertension. J Am Coll Cardiol 38:1137-1142
12. Sutendra G, Dromparis P, Kinnaird A, Stenson TH, Haromy A, Parker JM, McMurtry MS, Michelakis ED (2013) Mitochondrial activation by inhibition of PDKII suppresses HIF1a signaling and angiogenesis in cancer. Oncogene 32:1638-1650
13. Bruel A, Oxlund H, Nyengaard JR (2005) The total length of myocytes and capillaries, and total number of myocyte nuclei in the rat heart are time-dependently increased by growth hormone. Growth Horm IGF Res 15:256-264
14. Sutendra G, Dromparis P, Bonnet S, Haromy A, McMurtry MS, Bleackley RC, Michelakis ED (2011) Pyruvate dehydrogenase inhibition by the inflammatory cytokine TNFalpha contributes to the pathogenesis of pulmonary arterial hypertension. J Mol Med (Berl) 89:771-783
15. Sutendra G, Dromparis P, Wright P, Bonnet S, Haromy A, Hao Z, McMurtry MS, Michalak M, Vance JE, Sessa WC et al (2011) The role of Nogo and the mitochondria-endoplasmic reticulum unit in pulmonary hypertension. Sci Transl Med 3:88ra55
16. Ceconi C, Condorelli E, Quinzanini M, Rodella A, Ferrari R, Harris P (1989) Noradrenaline, atrial natriuretic peptide, bombesin and neurotensin in myocardium and blood of rats in congestive cardiac failure. Cardiovasc Res 23:674-682
17. Muders F, Elsner D (2000) Animal models of chronic heart failure. Pharmacol Res 41:605-612
18. Gomez-Arroyo JG, Farkas L, Alhussaini AA, Farkas D, Kraskauskas D, Voelkel NF, Bogaard HJ (2012) The monocrotaline model of pulmonary hypertension in perspective. Am J Physiol Lung Cell Mol Physiol 302:L363-L369
19. Nagendran J, Gurtu V, Fu DZ, Dyck JR, Haromy A, Ross DB, Rebeyka IM, Michelakis ED (2008) A dynamic and chamber-specific mitochondrial remodeling in right ventricular hypertrophy can be therapeutically targeted. J Thorac Cardiovasc Surg 136:168-178, 178 e161-163
20. Bonnet S, Archer SL, Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R, Lee CT, Lopaschuk GD, Puttagunta L, Harry G 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
21. Sutendra G, Bonnet S, Rochefort G, Haromy A, Folmes KD, Lopaschuk GD, Dyck JR, Michelakis ED (2010) Fatty acid oxidation and malonyl-CoA decarboxylase in the vascular remodeling of pulmonary hypertension. Sci Transl Med 2:44ra58
22. Dromparis P, Sutendra G, Michelakis ED (2010) The role of mitochondria in pulmonary vascular remodeling. J Mol Med (Berl) 88:1003-1010
23. Oikawa M, Kagaya Y, Otani H, Sakuma M, Demachi J, Suzuki J, Takahashi T, Nawata J, Ido T, Watanabe J et al (2005) Increased [18F]fluorodeoxyglucose accumulation in right ventricular free wall in patients with pulmonary hypertension and the effect of epoprostenol. J Am Coll Cardiol 45:1849-1855
24. 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
25. Salceda S, Caro J (1997) Hypoxia-inducible factor 1alpha (HIF-1alpha) protein is rapidly degraded by the ubiquitin-proteasome system under normoxic conditions. Its stabilization by hypoxia depends on redox-induced changes. J Biol Chem 272:22642-22647
26. 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
27. Brunelle JK, Bell EL, Quesada NM, Vercauteren K, Tiranti V, Zeviani M, Scarpulla RC, Chandel NS (2005) Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation. Cell Metab 1:409-414
28. Denko NC (2008) Hypoxia, HIF1 and glucose metabolism in the solid tumour. Nat Rev Cancer 8:705-713
29. Mansfield KD, Guzy RD, Pan Y, Young RM, Cash TP, Schumacker PT, Simon MC (2005) Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-alpha activation. Cell Metab 1:393-399
30. MacKenzie ED, Selak MA, Tennant DA, Payne LJ, Crosby S, Frederiksen CM, Watson DG, Gottlieb E (2007) Cell-permeating alpha-ketoglutarate derivatives alleviate pseudohypoxia in succinate dehydrogenase-deficient cells. Mol Cell Biol 27:3282-3289
31. Huang C, Zhang Z, Ding M, Li J, Ye J, Leonard SS, Shen HM, Butterworth L, Lu Y, Costa M et al (2000) Vanadate induces p53 transactivation through hydrogen peroxide and causes apoptosis. J Biol Chem 275:32516-32522
32. Wang S, Leonard SS, Ye J, Ding M, Shi X (2000) The role of hydroxyl radical as a messenger in Cr(VI)-induced p53 activation. Am J Physiol Cell Physiol 279:C868-C875
33. Xie S, Wang Q, Wu H, Cogswell J, Lu L, Jhanwar-Uniyal M, Dai W (2001) Reactive oxygen species-induced phosphorylation of p53 on serine 20 is mediated in part by polo-like kinase-3. J Biol Chem 276:36194-36199
34. Watcharasit P, Bijur GN, Song L, Zhu J, Chen X, Jope RS (2003) Glycogen synthase kinase-3beta (GSK3beta) binds to and promotes the actions of p53. J Biol Chem 278:48872-48879
35. Schmid T, Zhou J, Kohl R, Brune B (2004) p300 relieves p53-evoked transcriptional repression of hypoxia-inducible factor-1 (HIF-1). Biochem J 380:289-295
36. Vousden KH, Ryan KM (2009) p53 and metabolism. Nat Rev Cancer 9:691-700
37. Kaluzova M, Kaluz S, Lerman MI, Stanbridge EJ (2004) DNA damage is a prerequisite for p53-mediated proteasomal degradation of HIF-1alpha in hypoxic cells and downregulation of the hypoxia marker carbonic anhydrase IX. Mol Cell Biol 24:5757-5766
38. Ravi R, Mookerjee B, Bhujwalla ZM, Sutter CH, Artemov D, Zeng Q, Dillehay LE, Madan A, Semenza GL, Bedi A (2000) Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha. Genes Dev 14:34-44
39. Gudi R, Bowker-Kinley MM, Kedishvili NY, Zhao Y, Popov KM (1995) Diversity of the pyruvate dehydrogenase kinase gene family in humans. J Biol Chem 270:28989-28994
40. Gomez-Arroyo J, Mizuno S, Szczepanek K, Van Tassell B, Natarajan R, dos Remedios CG, Drake JI, Farkas L, Kraskauskas D, Wijesinghe DS et al (2012) Metabolic gene remodeling and mitochondrial dysfunction in failing right ventricular hypertrophy secondary to pulmonary arterial hypertension. Circ Heart Fail 6:136-144
41. Lundgrin EL, Park MM, Sharp J, Tang WH, Thomas JD, Asosingh K, Comhair SA, Difilippo FP, Neumann DR, Davis L et al (2013) Fasting 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography to detect metabolic changes in pulmonary arterial hypertension hearts over 1 year. Ann Am Thorac Soc 10:1-9
42. Bogaard HJ, Natarajan R, Mizuno S, Abbate A, Chang PJ, Chau VQ, Hoke NN, Kraskauskas D, Kasper M, Salloum FN et al (2010) Adrenergic receptor blockade reverses right heart remodeling and dysfunction in pulmonary hypertensive rats. Am J Respir Crit Care Med 182:652-660
43. Yasunari K, Maeda K, Nakamura M, Yoshikawa J (2002) Carvedilol inhibits pressure-induced increase in oxidative stress in coronary smooth muscle cells. Hypertens Res 25:419-425
44. Nakamura K, Kusano K, Nakamura Y, Kakishita M, Ohta K, Nagase S, Yamamoto M, Miyaji K, Saito H, Morita H et al (2002) Carvedilol decreases elevated oxidative stress in human failing myocardium. Circulation 105:2867-2871
45. Sano M, Minamino T, Toko H, Miyauchi H, Orimo M, Qin Y, Akazawa H, Tateno K, Kayama Y, Harada M et al (2007) p53-induced inhibition of Hif-1 causes cardiac dysfunction during pressure overload. Nature 446:444-448
46. Song H, Conte JV Jr, Foster AH, McLaughlin JS, Wei C (1999) Increased p53 protein expression in human failing myocardium. J Heart Lung Transplant 18:744-749
47. Wellen KE, Hatzivassiliou G, Sachdeva UM, Bui TV, Cross JR, Thompson CB (2009) ATP-citrate lyase links cellular metabolism to histone acetylation. Science 324:1076-1080
48. Tang Y, Zhao W, Chen Y, Zhao Y, Gu W (2008) Acetylation is indispensable for p53 activation. Cell 133:612-626