期刊
CIRCULATION RESEARCH
卷 95, 期 4, 页码 433-440出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.RES.0000138301.42713.18
关键词
gene expression; coronary artery disease; ischemia; stunning; hibernation
资金
- Medical Research Council [MC_U120084164] Funding Source: Medline
- NCRR NIH HHS [RR16592] Funding Source: Medline
- NHLBI NIH HHS [P01 HL59139, P01 HL69020, HL62442, HL072863, HL33107, HL33065] Funding Source: Medline
- NIA NIH HHS [AG 14121] Funding Source: Medline
- Medical Research Council [MC_U120084164] Funding Source: researchfish
- MRC [MC_U120084164] Funding Source: UKRI
Hibernating myocardium refers to chronically dysfunctional myocardium in patients with coronary artery disease in which cardiac viability is maintained and whose function improves after coronary revascularization. It is our hypothesis that long-term adaptive genomic mechanisms subtend the survival capacity of this ischemic myocardium. Therefore, the goal of this study was to determine whether chronic repetitive ischemia elicits a gene program of survival protecting hibernating myocardium against cell death. Accordingly, we measured the expression of survival genes in hibernating myocardium, both in patients surgically treated for hibernation and in a chronic swine model of repetitive ischemia reproducing the features of hibernation. Human hibernating myocardium was characterized by an upregulation of genes and corresponding proteins involved in anti-apoptosis (IAP), growth (VEGF, H11 kinase), and cytoprotection (HSP70, HIF-1alpha, GLUT1). In the swine model, the same genes and proteins were upregulated after repetitive ischemia, which was accompanied by a concomitant decrease in myocyte apoptosis. These changes characterize viable tissue, because they were not found in irreversibly injured myocardium. Our report demonstrates a novel mechanism by which the activation of an endogenous gene program of cell survival underlies the sustained viability of the hibernating heart. Potentially, promoting such a program offers a novel opportunity to salvage postmitotic tissues in conditions of ischemia.
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