title: Targeting energetic metabolism: a new frontier in the pathogenesis and treatment of pulmonary hypertension.
abstract: This perspective highlights advances in the understanding of the role of cellular metabolism in the pathogenesis of pulmonary hypertension. Insights gained in the past 20 years have revealed several similarities between the cellular processes underlying the pulmonary vascular remodeling in pulmonary hypertension and those seen in cancer processes. In line with these insights, there is increasing recognition that abnormal cellular metabolism, notably of aerobic glycolysis (the "Warburg effect"), the potential involvement of hypoxia-inducible factor in this process, and alterations in mitochondrial function, are key elements in the pathogenesis of this disease. The glycolytic shift may underlie the resistance to apoptosis and increased vascular cell proliferation, which are hallmarks of pulmonary hypertension. These investigations have led to novel approaches in the diagnosis and therapy of pulmonary hypertension.
authors.affiliation: Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, USA. rubin.tuder@ucdenver.edu
authors.forename: Rubin M
authors.initials: RM
authors.lastname: Tuder
authors.forename: Laura A
authors.initials: LA
authors.lastname: Davis
authors.forename: Brian B
authors.initials: BB
authors.lastname: Graham
mesh_terms: D017209:Apoptosis / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology*; D006019:Glycolysis / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy; D017380:Hypertrophy, Right Ventricular / Q000209:etiology; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008928:Mitochondria / Q000502:physiology
chemical_list: D051793:Hypoxia-Inducible Factor 1
references.citation: Am J Pathol. 1979 Jul;96(1):51-70
references.pmid: 464026
references.citation: Nat Rev Cancer. 2010 Apr;10(4):267-77
references.pmid: 20300106
references.citation: FASEB J. 2005 Jul;19(9):1178-80
references.pmid: 15897232
references.citation: Clin Chest Med. 2007 Mar;28(1):23-42, vii
references.pmid: 17338926
references.citation: Am J Respir Cell Mol Biol. 2005 Nov;33(5):425-31
references.pmid: 16234331
references.citation: Nat Rev Cancer. 2008 Dec;8(12):967-75
references.pmid: 18987634
references.citation: Am J Physiol Lung Cell Mol Physiol. 2007 Apr;292(4):L885-97
references.pmid: 17189321
references.citation: J Biol Chem. 1995 Dec 1;270(48):28989-94
references.pmid: 7499431
references.citation: Eur Respir J. 2011 Jun;37(6):1392-9
references.pmid: 20884740
references.citation: Nat Rev Cancer. 2003 Oct;3(10):721-32
references.pmid: 13130303
references.citation: Cardiovasc Res. 2008 Jul 15;79(2):259-68
references.pmid: 18499682
references.citation: J Clin Invest. 1998 Mar 1;101(5):927-34
references.pmid: 9486960
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 23;104(4):1342-7
references.pmid: 17227868
references.citation: Basic Res Cardiol. 2009 Mar;104(2):203-10
references.pmid: 19242641
references.citation: Br Heart J. 1957 Apr;19(2):279-86
references.pmid: 13413016
references.citation: Cell. 2011 Mar 4;144(5):646-74
references.pmid: 21376230
references.citation: Chest. 2010 Nov;138(5):1234-9
references.pmid: 21051399
references.citation: Am J Pathol. 2001 Jul;159(1):382-3
references.pmid: 11438486
references.citation: Cancer Cell. 2007 Jan;11(1):37-51
references.pmid: 17222789
references.citation: Biochem Pharmacol. 1988 Dec 15;37(24):4685-8
references.pmid: 2849454
references.citation: Eur Respir J. 2008 Dec;32(6):1639-51
references.pmid: 19043010
references.citation: J Am Coll Cardiol. 2005 Jun 7;45(11):1849-55
references.pmid: 15936618
references.citation: J Mol Med (Berl). 2010 Jan;88(1):47-60
references.pmid: 19949938
references.citation: Circulation. 2001 Aug 14;104(7):790-5
references.pmid: 11502704
references.citation: Am J Respir Crit Care Med. 2004 Mar 15;169(6):764-9
references.pmid: 14701708
references.citation: J Exp Biol. 2004 Aug;207(Pt 18):3189-200
references.pmid: 15299040
references.citation: J Pathol. 2001 Oct;195(3):367-74
references.pmid: 11673836
references.citation: Am J Hum Genet. 2001 Jan;68(1):92-102
references.pmid: 11115378
references.citation: Blood. 2005 Jan 15;105(2):659-69
references.pmid: 15374877
references.citation: Cell. 2007 Apr 6;129(1):111-22
references.pmid: 17418790
references.citation: Am J Respir Crit Care Med. 2011 Jan 15;183(2):152-6
references.pmid: 21242594
references.citation: Am J Physiol Lung Cell Mol Physiol. 2008 Dec;295(6):L1028-39
references.pmid: 18931051
references.citation: N Engl J Med. 2004 Sep 30;351(14):1425-36
references.pmid: 15459304
references.citation: Curr Hypertens Rep. 2005 Dec;7(6):407-11
references.pmid: 16386195
references.citation: Curr Hypertens Rep. 2003 Dec;5(6):459-65
references.pmid: 14594564
references.citation: J Cardiovasc Pharmacol. 2010 Aug;56(2):130-40
references.pmid: 20505524
references.citation: Mol Cell Biochem. 2006 Jul;287(1-2):1-11
references.pmid: 16670818
references.citation: Am J Pathol. 1980 Jul;100(1):151-78
references.pmid: 7395963
references.citation: Am J Pathol. 1994 Feb;144(2):275-85
references.pmid: 7508683
references.citation: Blood. 2011 May 5;117(18):4988-98
references.pmid: 21389314
references.citation: J Clin Invest. 2009 Mar;119(3):512-23
references.pmid: 19197140
references.citation: Chest. 1998 Sep;114(3 Suppl):225S-230S
references.pmid: 9741573
references.citation: Science. 2009 May 22;324(5930):1029-33
references.pmid: 19460998
references.citation: Nat Genet. 2000 Sep;26(1):81-4
references.pmid: 10973254
references.citation: J Cardiovasc Pharmacol. 2005 Oct;46(4):430-7
references.pmid: 16160593
references.citation: Am J Pathol. 2008 Mar;172(3):615-27
references.pmid: 18258847
references.citation: J Clin Invest. 2003 May;111(10):1519-27
references.pmid: 12750401
references.citation: Am J Hum Genet. 2000 Sep;67(3):737-44
references.pmid: 10903931
references.citation: Sci Transl Med. 2011 Jun 22;3(88):88ra55
references.pmid: 21697531
references.citation: Am J Respir Crit Care Med. 2010 Dec 15;182(12):1554-62
references.pmid: 20833821
references.citation: Circulation. 2006 Jun 6;113(22):2630-41
references.pmid: 16735674
references.citation: Physiol Rev. 2005 Jul;85(3):1093-129
references.pmid: 15987803
references.citation: N Engl J Med. 2005 Sep 29;353(13):1412-3
references.pmid: 16192491
references.citation: J Clin Invest. 2005 Oct;115(10):2811-21
references.pmid: 16200212
references.citation: J Am Coll Cardiol. 2009 Jun 30;54(1 Suppl):S10-S19
references.pmid: 19555853
references.citation: Am J Pathol. 2010 Mar;176(3):1130-8
references.pmid: 20110409
references.citation: Physiol Rev. 2010 Jan;90(1):207-58
references.pmid: 20086077
references.citation: Cell Metab. 2006 Mar;3(3):187-97
references.pmid: 16517406
references.citation: J Clin Invest. 2010 Mar;120(3):827-39
references.pmid: 20197624
references.citation: Am J Respir Crit Care Med. 2004 Dec 15;170(12):1340-8
references.pmid: 15361368
references.citation: Circ Res. 2006 Jun 23;98(12):1528-37
references.pmid: 16709899
references.citation: Biochem J. 1973 Aug;134(4):1067-81
references.pmid: 4762752
references.citation: Circ Res. 2004 Oct 15;95(8):830-40
references.pmid: 15375007
references.citation: Clin Sci (Lond). 2002 Aug;103 Suppl 48:210S-214S
references.pmid: 12193088
references.citation: Nat Rev Cancer. 2003 Jan;3(1):46-54
references.pmid: 12509766
references.citation: J Clin Invest. 1999 Mar;103(5):691-6
references.pmid: 10074486
references.citation: Circ Res. 2001 Jan 19;88(1):E2-E11
references.pmid: 11139485
references.citation: Respir Physiol Neurobiol. 2010 Dec 31;174(3):201-11
references.pmid: 20713189
references.citation: Nature. 2010 Jun 3;465(7298):562-4
references.pmid: 20520704
references.citation: J Clin Invest. 1999 Jan;103(2):291-9
references.pmid: 9916141
references.citation: Sci Transl Med. 2010 Aug 11;2(44):44ra58
references.pmid: 20702857
references.citation: Nat Rev Cancer. 2011 May;11(5):325-37
references.pmid: 21508971
references.citation: J Clin Invest. 2005 Jun;115(6):1479-91
references.pmid: 15931388
references.citation: Am J Pathol. 1994 Feb;144(2):286-95
references.pmid: 8311113
references.citation: FASEB J. 2001 Feb;15(2):427-38
references.pmid: 11156958
references.citation: Cell. 2000 Jan 7;100(1):57-70
references.pmid: 10647931
references.citation: Nat Cell Biol. 2011 Aug 14;13(9):1146-52
references.pmid: 21841792
references.citation: Science. 2009 Apr 10;324(5924):261-5
references.pmid: 19359588
references.citation: PLoS Genet. 2005 Jul;1(1):72-80
references.pmid: 16103922
references.citation: Nat Med. 2002 Oct;8(10):1129-35
references.pmid: 12244304
references.citation: J Mol Med (Berl). 2010 Oct;88(10):1011-20
references.pmid: 20820751
references.citation: Cell Metab. 2006 Mar;3(3):177-85
references.pmid: 16517405
references.citation: Am J Pathol. 2006 Feb;168(2):659-69
references.pmid: 16436679
references.citation: Am J Respir Crit Care Med. 2009 Oct 15;180(8):780-7
references.pmid: 19628780
references.citation: Chest. 1998 Jul;114(1 Suppl):1S-6S
references.pmid: 9676599
references.citation: Am J Respir Crit Care Med. 2010 Nov 1;182(9):1153-60
references.pmid: 20581168
references.citation: J Clin Invest. 2000 Sep;106(6):733-8
references.pmid: 10995781