© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Brief episode of ischemia activates protective genetic program in rat heart: a gene chip study
aHeart Institute, Good Samaritan Hospital, Los Angeles, CA 90017, USA
bDepartment of Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA
cDepartment of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA
dDepartment of Biochemistry and Molecular Biology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA
eInstitute for Genetic Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA
* Corresponding author. Heart Institute, Good Samaritan Hospital, 1225 Wilshire Boulevard, Los Angeles, CA 90017, USA. Tel.: +1-213-977-4194; fax: +1-213-977-4107. simkhovi{at}hsc.usc.edu
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 
protein compared to the NI tissue. The majority of mRNAs whose levels increased following brief ischemia were of a protective nature. Conclusion: 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.
KEYWORDS Heart; Gene expression; Ischemia; Preconditioning
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