Brief episode of ischemia activates protective genetic program in rat heart: a gene chip study

被引:51
作者
Simkhovich, BZ
Marjoram, P
Poizat, C
Kedes, L
Kloner, RA
机构
[1] Hosp Good Samaritan, Inst Heart, Los Angeles, CA 90017 USA
[2] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA
[3] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA
[4] Univ So Calif, Keck Sch Med, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA
[5] Univ So Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90033 USA
基金
美国国家卫生研究院;
关键词
heart; gene expression; ischemia; preconditioning;
D O I
10.1016/S0008-6363(03)00399-7
中图分类号
R5 [内科学];
学科分类号
1002 [临床医学]; 100201 [内科学];
摘要
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 a 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. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:450 / 459
页数:10
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