title: Metabolic gene expression in fetal and failing human heart.
abstract: 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.
  
  
  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-alpha and -beta, 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.
authors.affiliation: Division of Cardiology, University of Texas-Houston Medical School, Houston, TX 77030, USA.
authors.forename: P
authors.initials: P
authors.lastname: Razeghi
authors.forename: M E
authors.initials: ME
authors.lastname: Young
authors.forename: J L
authors.initials: JL
authors.lastname: Alcorn
authors.forename: C S
authors.initials: CS
authors.lastname: Moravec
authors.forename: O H
authors.initials: OH
authors.lastname: Frazier
authors.forename: H
authors.initials: H
authors.lastname: Taegtmeyer
mesh_terms: D042964:Acyl-CoA Dehydrogenase; D000328:Adult; D009320:Atrial Natriuretic Factor / Q000235:genetics; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002950:Citrate (si)-Synthase / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics*; D044943:Fatty Acid Desaturases / Q000235:genetics; D005260:Female; D005318:Fetal Heart / Q000378:metabolism*; D005333:Fetus; D015870:Gene Expression; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D006019:Glycolysis / Q000235:genetics; D006333:Heart Failure / Q000235:genetics*; D006801:Humans; D007473:Ion Channels; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D024101:Mitochondrial Proteins; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D009124:Muscle Proteins; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018995:Myosin Heavy Chains / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
chemical_list: D002352:Carrier Proteins; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D020033:Protein Isoforms; D011506:Proteins; D012333:RNA, Messenger; C495677:SLC2A1 protein, human; C495692:SLC2A4 protein, human; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D009320:Atrial Natriuretic Factor; D044943:Fatty Acid Desaturases; D042964:Acyl-CoA Dehydrogenase; D002334:Carnitine O-Palmitoyltransferase; D002950:Citrate (si)-Synthase; D018995:Myosin Heavy Chains