Transcriptional changes following restoration of SERCA2a levels in failing rat hearts.
Heart failure is characterized at the cellular level by impaired contractility and abnormal Ca2+ homeostasis. We have previously shown that restoration of a key enzyme that controls intracellular Ca(2+) handling, the sarcoplasmic reticulum Ca2+ ATPase (SERCA2a), induces functional improvement in heart failure. We used high-density oligonucleotide arrays to explore the effects of gene transfer of SERCA2a on genetic reprogramming in a model of heart failure. A total of 1,300 transcripts were identified to be unmodified by the effect of virus alone. Of those, 251 transcripts were found to be up- or down-regulated upon failure. A total of 51 transcripts which were either up--(27) or down--(24) regulated in heart failure were normalized to the nonfailing levels by the restoration of SERCA2a by gene transfer. The microarray analysis identified new genes following SERCA2a restoration in heart failure, which will give us insights into their role in the normalization of multiple pathways within the failing cell.
Del Monte
Federica
F
Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Dalal
Rishikesh
R
Tabchy
Adel
A
Couget
Jennifer
J
Bloch
Kenneth D
KD
Peterson
Randall
R
Hajjar
Roger J
RJ
D000818:Animals; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D002303:Cardiac Output, Low / Q000235:genetics* / Q000378:metabolism*; D015536:Down-Regulation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006706:Homeostasis; D006801:Humans; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D014158:Transcription, Genetic / Q000235:genetics*; D015854:Up-Regulation
D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium