Program of cell survival underlying human and experimental hibernating myocardium

Christophe Depre, Song Jung Kim, Anna S. John, Yanhong Huang, Ornella E. Rimoldi, John R. Pepper, Gilles D. Dreyfus, Vinciane Gaussin, Dudley J. Pennell, Dorothy E. Vatner, Paolo G. Camici, Stephen F. Vatner

Research output: Contribution to journalArticle

Abstract

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-1α, 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.

Original languageEnglish
Pages (from-to)433-440
Number of pages8
JournalCirculation Research
Volume95
Issue number4
DOIs
Publication statusPublished - Aug 20 2004

Keywords

  • Coronary artery disease
  • Gene expression
  • Hibernation
  • Ischemia
  • Stunning

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Depre, C., Kim, S. J., John, A. S., Huang, Y., Rimoldi, O. E., Pepper, J. R., Dreyfus, G. D., Gaussin, V., Pennell, D. J., Vatner, D. E., Camici, P. G., & Vatner, S. F. (2004). Program of cell survival underlying human and experimental hibernating myocardium. Circulation Research, 95(4), 433-440. https://doi.org/10.1161/01.RES.0000138301.42713.18