Circulation. 2001;104:2923-2931
doi: 10.1161/hc4901.100526
doi: 10.1161/hc4901.100526
(Circulation. 2001;104:2923.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Metabolic Gene Expression in Fetal and Failing Human Heart
From the Division of Cardiology (P.R., M.E.Y., H.T.) and the Department of Pediatrics (J.L.A.), University of Texas-Houston Medical School, and St Luke’s Episcopal Hospital and Texas Heart Institute (O.H.F., H.T.), Houston, Tex; and the Center for Anesthesiology Research, Cleveland Clinic Foundation, Cleveland, Ohio (C.S.M.).
Correspondence to Heinrich Taegtmeyer, MD, DPhil, Department of Internal Medicine, Division of Cardiology, University of Texas-Houston Medical School, 6431 Fannin, MSB 1.246, Houston, TX 77030. E-mail heinrich.taegtmeyer{at}uth.tmc.edu
Background— Previous studies suggest that the failing heart reactivates fetal genes and reverts to a fetal pattern of energy substrate metabolism. We tested this hypothesis by examining metabolic gene expression profiles in the fetal, nonfailing, and failing human heart.
Methods and Results— Human left ventricular tissue (apex) was obtained from 9 fetal, 10 nonfailing, and 10 failing adult hearts. Using quantitative reverse transcription-polymerase chain reaction, we measured transcript levels of atrial natriuretic factor, myosin heavy chain-
and -ß, and 13 key regulators of energy substrate metabolism, of which 3 are considered "adult" isoforms (GLUT4, mGS, mCPT-I) and 3 are considered "fetal" isoforms (GLUT1, lGS, and lCPT-I), primarily through previous studies in rodent models. Compared with the nonfailing adult heart, steady-state mRNA levels of atrial natriuretic factor were increased in both the fetal and the failing heart. The 2 myosin heavy chain isoforms showed the highest expression level in the nonfailing heart. Transcript levels of most of the metabolic genes were higher in the nonfailing heart than the fetal heart. Adult isogenes predominated in all groups and always showed a greater induction than the fetal isogenes in the nonfailing heart compared with the fetal heart. In the failing heart, the expression of metabolic genes decreased to the same levels as in the fetal heart.
Conclusions— In the human heart, metabolic genes exist as constitutive and inducible forms. The failing adult heart reverts to a fetal metabolic gene profile by downregulating adult gene transcripts rather than by upregulating fetal genes.
Key Words: heart failure • fetal heart • genes • polymerase chain reaction • metabolism
This article has been cited by other articles:
 |
|
 |
|
  V. Soukoulis, J. B. Dihu, M. Sole, S. D. Anker, J. Cleland, G. C. Fonarow, M. Metra, E. Pasini, T. Strzelczyk, H. Taegtmeyer, et al. Micronutrient deficiencies an unmet need in heart failure. J. Am. Coll. Cardiol., October 27, 2009; 54(18): 1660 - 1673. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Hue and H. Taegtmeyer The Randle cycle revisited: a new head for an old hat Am J Physiol Endocrinol Metab, September 1, 2009; 297(3): E578 - E591. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Garnier, J. Zoll, D. Fortin, B. N'Guessan, F. Lefebvre, B. Geny, B. Mettauer, V. Veksler, and R. Ventura-Clapier Control by Circulating Factors of Mitochondrial Function and Transcription Cascade in Heart Failure: A Role for Endothelin-1 and Angiotensin II Circ Heart Fail, July 1, 2009; 2(4): 342 - 350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Serpillon, B. C. Floyd, R. S. Gupte, S. George, M. Kozicky, V. Neito, F. Recchia, W. Stanley, M. S. Wolin, and S. A. Gupte Superoxide production by NAD(P)H oxidase and mitochondria is increased in genetically obese and hyperglycemic rat heart and aorta before the development of cardiac dysfunction. The role of glucose-6-phosphate dehydrogenase-derived NADPH Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H153 - H162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Stuck, M. Lenski, M. Bohm, and U. Laufs Metabolic Switch and Hypertrophy of Cardiomyocytes following Treatment with Angiotensin II Are Prevented by AMP-activated Protein Kinase J. Biol. Chem., November 21, 2008; 283(47): 32562 - 32569. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. D. Akavia and D. Benayahu Meta-analysis and profiling of cardiac expression modules Physiol Genomics, November 12, 2008; 35(3): 305 - 315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Y. Boateng and P. H. Goldspink Assembly and maintenance of the sarcomere night and day Cardiovasc Res, March 1, 2008; 77(4): 667 - 675. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Witteles and M. B. Fowler Insulin-Resistant Cardiomyopathy: Clinical Evidence, Mechanisms, and Treatment Options J. Am. Coll. Cardiol., January 15, 2008; 51(2): 93 - 102. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Page, R. Young, V. Iyer, G. Suzuki, M. Lis, L. Korotchkina, M. S. Patel, K. M. Blumenthal, J. A. Fallavollita, and J. M. Canty Jr Persistent Regional Downregulation in Mitochondrial Enzymes and Upregulation of Stress Proteins in Swine With Chronic Hibernating Myocardium Circ. Res., January 4, 2008; 102(1): 103 - 112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sebastiani, C. Giordano, C. Nediani, C. Travaglini, E. Borchi, M. Zani, M. Feccia, M. Mancini, V. Petrozza, A. Cossarizza, et al. Induction of Mitochondrial Biogenesis Is a Maladaptive Mechanism in Mitochondrial Cardiomyopathies J. Am. Coll. Cardiol., October 2, 2007; 50(14): 1362 - 1369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Guellich, T. Damy, Y. Lecarpentier, M. Conti, V. Claes, J.-L. Samuel, J. Quillard, J.-L. Hebert, T. Pineau, and C. Coirault Role of oxidative stress in cardiac dysfunction of PPAR{alpha}-/- mice Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H93 - H102. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. D. Lewandowski, J. M. O'Donnell, T. D. Scholz, N. Sorokina, and P. M. Buttrick Recruitment of NADH shuttling in pressure-overloaded and hypertrophic rat hearts Am J Physiol Cell Physiol, May 1, 2007; 292(5): C1880 - C1886. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Neubauer The Failing Heart -- An Engine Out of Fuel N. Engl. J. Med., March 15, 2007; 356(11): 1140 - 1151. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Taegtmeyer and K. Ballal No Low-Fat Diet for the Failing Heart? Circulation, November 14, 2006; 114(20): 2092 - 2093. [Full Text] [PDF]
|
|
|
|
 |
|
 E. E. Morgan, M. P. Chandler, M. E. Young, T. A. McElfresh, T. A. Kung, J. H. Rennison, K.-Y. Tserng, B. D. Hoit, and W. C. Stanley Dissociation between gene and protein expression of metabolic enzymes in a rodent model of heart failure Eur J Heart Fail, November 1, 2006; 8(7): 687 - 693. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Murray, C. A. Lygate, M. A. Cole, C. A. Carr, G. K. Radda, S. Neubauer, and K. Clarke Insulin resistance, abnormal energy metabolism and increased ischemic damage in the chronically infarcted rat heart Cardiovasc Res, July 1, 2006; 71(1): 149 - 157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Liao, S. Takashima, H. Zhao, Y. Asano, Y. Shintani, T. Minamino, J. Kim, M. Fujita, M. Hori, and M. Kitakaze Control of plasma glucose with alpha-glucosidase inhibitor attenuates oxidative stress and slows the progression of heart failure in mice Cardiovasc Res, April 1, 2006; 70(1): 107 - 116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Luptak, J. A. Balschi, Y. Xing, T. C. Leone, D. P. Kelly, and R. Tian Decreased Contractile and Metabolic Reserve in Peroxisome Proliferator-Activated Receptor-{alpha}-Null Hearts Can Be Rescued by Increasing Glucose Transport and Utilization Circulation, October 11, 2005; 112(15): 2339 - 2346. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wiggers, H. Norrelund, S. S. Nielsen, N. H. Andersen, J. E. Nielsen-Kudsk, J. S. Christiansen, T. T. Nielsen, N. Moller, and H. E. Botker Influence of insulin and free fatty acids on contractile function in patients with chronically stunned and hibernating myocardium Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H938 - H946. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Dewald, S. Sharma, J. Adrogue, R. Salazar, G. D. Duerr, J. D. Crapo, M. L. Entman, and H. Taegtmeyer Downregulation of Peroxisome Proliferator-Activated Receptor-{alpha} Gene Expression in a Mouse Model of Ischemic Cardiomyopathy Is Dependent on Reactive Oxygen Species and Prevents Lipotoxicity Circulation, July 19, 2005; 112(3): 407 - 415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. C. Stanley, F. A. Recchia, and G. D. Lopaschuk Myocardial Substrate Metabolism in the Normal and Failing Heart Physiol Rev, July 1, 2005; 85(3): 1093 - 1129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Lionetti, A. Linke, M. P. Chandler, M. E. Young, M. S. Penn, S. Gupte, C. d'Agostino, T. H. Hintze, W. C. Stanley, and F. A. Recchia Carnitine palmitoyl transferase-I inhibition prevents ventricular remodeling and delays decompensation in pacing-induced heart failure Cardiovasc Res, June 1, 2005; 66(3): 454 - 461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Wellner, R. Dechend, J.-K. Park, E. Shagdarsuren, N. Al-Saadi, T. Kirsch, P. Gratze, W. Schneider, S. Meiners, A. Fiebeler, et al. Cardiac gene expression profile in rats with terminal heart failure and cachexia Physiol Genomics, February 10, 2005; 20(3): 256 - 267. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Nemoto, P. Razeghi, M. Ishiyama, G. De Freitas, H. Taegtmeyer, and B. A. Carabello PPAR-{gamma} agonist rosiglitazone ameliorates ventricular dysfunction in experimental chronic mitral regurgitation Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H77 - H82. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. SHARMA, J. V. ADROGUE, L. GOLFMAN, I. URAY, J. LEMM, K. YOUKER, G. P. NOON, O. H FRAZIER, and H. TAEGTMEYER Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart FASEB J, November 1, 2004; 18(14): 1692 - 1700. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. N. Lavrentyev, D. He, and G. A. Cook Expression of genes participating in regulation of fatty acid and glucose utilization and energy metabolism in developing rat hearts Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H2035 - H2042. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Chandler, J. Kerner, H. Huang, E. Vazquez, A. Reszko, W. Z. Martini, C. L. Hoppel, M. Imai, S. Rastogi, H. N. Sabbah, et al. Moderate severity heart failure does not involve a downregulation of myocardial fatty acid oxidation Am J Physiol Heart Circ Physiol, October 1, 2004; 287(4): H1538 - H1543. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Nikolaidis, D. Elahi, T. Hentosz, A. Doverspike, R. Huerbin, L. Zourelias, C. Stolarski, Y.-t. Shen, and R. P. Shannon Recombinant Glucagon-Like Peptide-1 Increases Myocardial Glucose Uptake and Improves Left Ventricular Performance in Conscious Dogs With Pacing-Induced Dilated Cardiomyopathy Circulation, August 24, 2004; 110(8): 955 - 961. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Ingwall and R. G. Weiss Is the Failing Heart Energy Starved?: On Using Chemical Energy to Support Cardiac Function Circ. Res., July 23, 2004; 95(2): 135 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Sutinen, K. Kannisto, E. Korsheninnikova, R. M. Fisher, E. Ehrenborg, T. Nyman, A. Virkamaki, T. Funahashi, Y. Matsuzawa, H. Vidal, et al. Effects of rosiglitazone on gene expression in subcutaneous adipose tissue in highly active antiretroviral therapy-associated lipodystrophy Am J Physiol Endocrinol Metab, June 1, 2004; 286(6): E941 - E949. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Bartelds, J. Takens, G. B. Smid, V. A. Zammit, C. Prip-Buus, J. R. G. Kuipers, and F. R. van der Leij Myocardial carnitine palmitoyltransferase I expression and long-chain fatty acid oxidation in fetal and newborn lambs Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2243 - H2248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hansson, N. Hance, E. Dufour, A. Rantanen, K. Hultenby, D. A. Clayton, R. Wibom, and N.-G. Larsson A switch in metabolism precedes increased mitochondrial biogenesis in respiratory chain-deficient mouse hearts PNAS, March 2, 2004; 101(9): 3136 - 3141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ventura-Clapier, A. Garnier, and V. Veksler Energy metabolism in heart failure J. Physiol., February 15, 2004; 555(1): 1 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Santalucia, M. Christmann, M. H Yacoub, and N. J Brand Hypertrophic agonists induce the binding of c-Fos to an AP-1 site in cardiac myocytes: implications for the expression of GLUT1 Cardiovasc Res, September 1, 2003; 59(3): 639 - 648. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Teshima, M. Akao, S. P. Jones, and E. Marban Uncoupling Protein-2 Overexpression Inhibits Mitochondrial Death Pathway in Cardiomyocytes Circ. Res., August 8, 2003; 93(3): 192 - 200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. P. Cappola, L. Cope, A. Cernetich, L. A. Barouch, K. Minhas, R. A. Irizarry, G. Parmigiani, S. Durrani, T. Lavoie, E. P. Hoffman, et al. Deficiency of different nitric oxide synthase isoforms activates divergent transcriptional programs in cardiac hypertrophy Physiol Genomics, June 24, 2003; 14(1): 25 - 34. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Sheikh-Hamad, R. Bick, G.-Y. Wu, B. M. Christensen, P. Razeghi, B. Poindexter, H. Taegtmeyer, A. Wamsley, R. Padda, M. Entman, et al. Stanniocalcin-1 is a naturally occurring L-channel inhibitor in cardiomyocytes: relevance to human heart failure Am J Physiol Heart Circ Physiol, June 5, 2003; 285(1): H442 - H448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Irie, I. B. Krukenkamp, J. F. F. Brinkmann, G. R. Gaudette, A. E. Saltman, W. Jou, J. F. C. Glatz, N. A. Abumrad, and A. Ibrahimi Myocardial recovery from ischemia is impaired in CD36-null mice and restored by myocyte CD36 expression or medium-chain fatty acids PNAS, May 27, 2003; 100(11): 6819 - 6824. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Taegtmeyer Switching Metabolic Genes to Build a Better Heart Circulation, October 15, 2002; 106(16): 2043 - 2045. [Full Text] [PDF]
|
|
|
|
|
|
J. C. Osorio, W. C. Stanley, A. Linke, M. Castellari, Q. N. Diep, A. R. Panchal, T. H. Hintze, G. D. Lopaschuk, and F. A. Recchia Impaired Myocardial Fatty Acid Oxidation and Reduced Protein Expression of Retinoid X Receptor-{alpha} in Pacing-Induced Heart Failure Circulation, July 30, 2002; 106(5): 606 - 612. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Razeghi, M. E. Young, T. C. Cockrill, O. H. Frazier, and H. Taegtmeyer Downregulation of Myocardial Myocyte Enhancer Factor 2C and Myocyte Enhancer Factor 2C-Regulated Gene Expression in Diabetic Patients With Nonischemic Heart Failure Circulation, July 23, 2002; 106(4): 407 - 411. [Abstract] [Full Text] [PDF]
|
|