Brief episode of ischemia activates protective genetic program in rat heart: a gene chip study.
OBJECTIVE
Brief episodes of ischemia of 20 min or less have the potential to protect the heart. Such episodes are associated primarily with reversible ischemic injury yet they induce changes in gene expression. The purpose of the study was to determine whether activation of protective genes takes place within 4 h following a brief episode of ischemia that would mimic angina pectoris.


METHODS
Three groups of rats were studied. In the control (Ctrl) group, hearts were immediately excised following anesthesia; in the sham-operated (SO) group, opened-chest rats received 4 h and 20 min of no intervention; and in the group subjected to ischemia (SI) hearts received 20 min of proximal coronary occlusion followed by 4 h of reperfusion. Hearts from the SI group were divided into nonischemic (NI) and ischemic (Isc) areas. Changes in gene expression pattern were analyzed by using Affymetrix Gene Chips.


RESULTS
Ischemia led to strong upregulation of mRNA transcripts for heat shock proteins 70, 27, 105, 86 and 40 kDa, vascular endothelial growth factor, brain-derived neurotrophic factor, plasminogen activator inhibitor-1, activating transcription factor 3, B-cell translocation gene 2, and growth arrest and DNA damage inducible 45 alpha protein compared to the NI tissue. The majority of mRNAs whose levels increased following brief ischemia were of a protective nature.


CONCLUSIONS
Genetic reprogramming emerging during or following brief episodes of ischemia that simulate angina, can be characterized as protective in nature. Developing new therapeutic strategies aimed to promote this protective response represents a legitimate target for future research.
Simkhovich
Boris Z
BZ
Heart Institute, Good Samaritan Hospital, Los Angeles, CA 90017, USA.simkhovi@hsc.usc.edu
Marjoram
Paul
P
Poizat
Coralie
C
Kedes
Larry
L
Kloner
Robert A
RA
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern / Q000379:methods; D040501:Calgranulin A / Q000235:genetics; D040502:Calgranulin B / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006360:Heat-Shock Proteins; D019157:Ischemic Preconditioning, Myocardial; D008969:Molecular Sequence Data; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D040501:Calgranulin A; D040502:Calgranulin B; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486114:Hspb1 protein, rat; D009363:Neoplasm Proteins; D017395:Plasminogen Activator Inhibitor 1