Age-associated changes in cardiac gene expression after preconditioning.
BACKGROUND
Cardiac protection afforded by ischemic preconditioning (IPC) and anesthetic preconditioning (APC) are significantly reduced in the senescent myocardium. The authors hypothesized that age would differentially modulate gene expression induced by IPC and APC in vivo.


METHODS
Affymetrix RAT EXON ST 1.0 gene chips (Affymetrix, Santa Clara, CA) were used to explore the transcriptional response to IPC and APC in Fisher 344 male rats (young, 3-5 months, and old, 20-24 months, respectively). Both cohorts, young and old, were divided into three groups: (1) sham control, (2) IPC, and (3) APC. After a total of 90 min, the heart was removed, and the total RNA and protein were extracted.


RESULTS
Thirty-one transcripts were increased in the young animals subjected to IPC, particularly transcriptional regulators (Atf3, Egr-1, Btg2, Egr2), cytokines (interleukin 6, CSF1, Myd88), chemokines (Cxcl10, Ccl2, Ccl7), regulators of growth and inflammation (Reg3g, Hamp), remodeling and cell adhesion migration (Cyr61, Tfpi2, Timp1), regulators of apoptosis/cell death (Birc3, Arntl, Hamp, Phlda1), and cell cycle control/DNA repairs (Rrad, Gadd45b, Gadd45g). In contrast, only one transcript increased (Atf3) in the old animals subjected to IPC. No changes in gene expression were found in the young or the old animals subjected to APC.


CONCLUSIONS
Early-phase IPC and APC induced different genomic responses. The absence of detectable changes associated with early-phase APC suggests a posttranscriptional or posttranslational mechanism. The absence of a genomic response in the senescent myocardium (except for IPC-induced Atf3) could underlie the failure of IPC to provide any cardiac protective benefit to older animals.
Department of Anesthesiology, Stony Brook University School of Medicine, New York 11794, USA. lixliu@notes.cc.sunysb.edu
Lixin
L
Liu
Jiang
J
Zhu
Peter S A
PS
Glass
Peter R
PR
Brink
Ira J
IJ
Rampil
Mario J
MJ
Rebecchi
D000367:Age Factors; D000818:Animals; D015153:Blotting, Western; D020869:Gene Expression Profiling; D006439:Hemodynamics; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction