Regulation of gene expression in rats with heart failure treated with the thyroid hormone analog 3,5-diiodothyropropionic acid (DITPA) and the combination of DITPA and captopril.
We have used an oligonucleotide microarray to identify genes that are affected by congestive heart failure and those influenced by treatment with DITPA and DITPA in combination with captopril using a rat postinfarction model. The most striking result when comparing heart failure to sham operation was that all of the mitochondrial and metabolic enzymes affected were down regulated. When comparing heart failure with DITPA treatment, most of the down regulated metabolic genes were returned toward normal. When comparing heart failure with heart failure animals treated with DITPA and captopril, metabolic enzymes were no longer significantly downregulated. DITPA treatment and the combination of DITPA and captopril show that the metabolic enzymes were no longer down regulated. This represents a substantial improvement in the energy- generating capacity of the heart. These results indicate that the actions of DITPA and the combination of DITPA and captopril in heart failure can be partially explained by differences in gene activation.
Maitra
Niranjan
N
Department of Sarver Heart Center, University of Arizona, Tucson, AZ, USA.
Adamson
Cynthia
C
Greer
Kevin
K
Klewer
Scott
S
Hoying
James
J
Bahl
Joseph J
JJ
Goldman
Steven
S
Morkin
Eugene
E
D000818:Animals; D002216:Captopril / Q000494:pharmacology* / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use; D004104:Diiodothyronines / Q000494:pharmacology* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005786:Gene Expression Regulation / Q000187:drug effects*; D024601:Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+) / Q000235:genetics; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics; D009203:Myocardial Infarction / Q000188:drug therapy / Q000503:physiopathology; D011422:Propionates / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation; D016277:Ventricular Function, Left / Q000187:drug effects
D002316:Cardiotonic Agents; D004104:Diiodothyronines; D024101:Mitochondrial Proteins; D011422:Propionates; C082182:3,5-diiodothyropropionic acid; D002216:Captopril; D024601:Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+); D025261:Mitochondrial Proton-Translocating ATPases