Circulation (New York, N.Y.), 2001-12, Vol.104 (24), p.2923-2931
2001
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Metabolic gene expression in fetal and failing human heart
- Ist Teil von
- Circulation (New York, N.Y.), 2001-12, Vol.104 (24), p.2923-2931
- Ort / Verlag
- Hagerstown, MD: Lippincott Williams & Wilkins
- Erscheinungsjahr
- 2001
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. 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. 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0009-7322eISSN: 1524-4539DOI: 10.1161/hc4901.100526Titel-ID: cdi_proquest_miscellaneous_72338809
- Format
- –
- Schlagworte
- Acyl-CoA Dehydrogenase, Adult, Atrial Natriuretic Factor - genetics, Biological and medical sciences, Cardiology. Vascular system, Carnitine O-Palmitoyltransferase - genetics, Carrier Proteins - genetics, Citrate (si)-Synthase - genetics, Energy Metabolism - genetics, Fatty Acid Desaturases - genetics, Female, Fetal Heart - metabolism, Fetus, Gene Expression, Gene Expression Profiling, Gene Expression Regulation, Developmental, Glucose Transporter Type 1, Glucose Transporter Type 4, Glycolysis - genetics, Heart, Heart Failure - genetics, Heart failure, cardiogenic pulmonary edema, cardiac enlargement, Humans, Ion Channels, Male, Medical sciences, Membrane Transport Proteins, Middle Aged, Mitochondrial Proteins, Monosaccharide Transport Proteins - genetics, Muscle Proteins, Myocardium - metabolism, Myocardium - pathology, Myosin Heavy Chains - genetics, Protein Isoforms - genetics, Proteins - genetics, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger - genetics, RNA, Messenger - metabolism, Uncoupling Protein 2, Uncoupling Protein 3