Published online before print July 8, 2004, doi: 10.1161/01.RES.0000138301.42713.18
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on September 17, 2003
Revised on June 25, 2004
Accepted on June 28, 2004
Program of Cell Survival Underlying Human and Experimental Hibernating Myocardium
Christophe Depre ;
From the Department of Cell Biology and Molecular Medicine and the Cardiovascular Research Institute (C.D., S.-J.K., Y.H.H., V.G., D.E.V., S.F.V.), University of Medicine and Dentistry New Jersey, Newark; National Heart and Lung Institute (A.S.J., O.E.R., J.R.P., G.D.D., D.J.P., P.G.C.), Imperial College, London, UK; and Medical Research Council Clinical Sciences Centre (O.E.R., P.G.C.), London, UK.
* To whom correspondence should be addressed. E-mail: vatnersf{at}umdnj.edu.
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-1
, 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.
Key words: gene expression • coronary artery disease • ischemia • stunning • hibernation
This article has been cited by other articles:
 |
|
 |
|
  X. Sui, D. Li, H. Qiu, V. Gaussin, and C. Depre Activation of the Bone Morphogenetic Protein Receptor by H11Kinase/Hsp22 Promotes Cardiac Cell Growth and Survival Circ. Res., April 10, 2009; 104(7): 887 - 895. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Prasad, A. Clerk, T. E. Cullingford, A. W.Y. Chen, T. J. Kemp, T. M. Cannell, M. R. Cowie, and M. Petrou Gene expression profiling of human hibernating myocardium: Increased expression of B-type natriuretic peptide and proenkephalin in hypocontractile vs normally-contracting regions of the heart Eur J Heart Fail, December 1, 2008; 10(12): 1177 - 1180. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Heusch, K. Boengler, and R. Schulz Cardioprotection: Nitric Oxide, Protein Kinases, and Mitochondria Circulation, November 4, 2008; 118(19): 1915 - 1919. [Full Text] [PDF]
|
|
|
|
 |
|
 Y. C. Jin, K. J. Kim, Y. M. Kim, Y. M. Ha, H. J. Kim, U. J. Yun, K. H. Bae, Y. S. Kim, S. S. Kang, H. G. Seo, et al. Anti-Apoptotic Effect of Magnolol in Myocardial Ischemia and Reperfusion Injury Requires Extracellular Signal-Regulated Kinase1/2 Pathways in Rat In Vivo Experimental Biology and Medicine, October 1, 2008; 233(10): 1280 - 1288. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Hedhli, P. Lizano, C. Hong, L. F. Fritzky, S. K. Dhar, H. Liu, Y. Tian, S. Gao, K. Madura, S. F. Vatner, et al. Proteasome inhibition decreases cardiac remodeling after initiation of pressure overload Am J Physiol Heart Circ Physiol, October 1, 2008; 295(4): H1385 - H1393. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Qiu, H. Dai, K. Jain, R. Shah, C. Hong, J. Pain, B. Tian, D. E. Vatner, S. F. Vatner, and C. Depre Characterization of a Novel Cardiac Isoform of the Cell Cycle-related Kinase That Is Regulated during Heart Failure J. Biol. Chem., August 8, 2008; 283(32): 22157 - 22165. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Kuner, A. S. Barth, M. Ruschhaupt, A. Buness, L. Zwermann, E. Kreuzer, G. Steinbeck, A. Poustka, H. Sultmann, and M. Nabauer Genomic analysis reveals poor separation of human cardiomyopathies of ischemic and nonischemic etiologies Physiol Genomics, June 1, 2008; 34(1): 88 - 94. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. May, D. Gilon, V. Djonov, A. Itin, A. Lazarus, O. Gordon, C. Rosenberger, and E. Keshet Transgenic system for conditional induction and rescue of chronic myocardial hibernation provides insights into genomic programs of hibernation PNAS, January 8, 2008; 105(1): 282 - 287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. F. Kelly, W. Sluiter, and E. O. McFalls Hibernating Myocardium: Is the Program to Survive a Pathway to Failure? Circ. Res., January 4, 2008; 102(1): 3 - 5. [Full Text] [PDF]
|
|
|
|
|
|
B. Page, R. Young, V. Iyer, G. Suzuki, M. Lis, L. Korotchkina, M. S. Patel, K. M. Blumenthal, J. A. Fallavollita, and J. M. Canty Jr Persistent Regional Downregulation in Mitochondrial Enzymes and Upregulation of Stress Proteins in Swine With Chronic Hibernating Myocardium Circ. Res., January 4, 2008; 102(1): 103 - 112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Schneider, K. Jaquet, R. Malisius, S. Geidel, E. Bahlmann, S. Boczor, T. Rau, M. Antz, K.-H. Kuck, and K. Krause Attenuation of cardiac remodelling by endocardial injection of erythropoietin: ultrasonic strain-rate imaging in a model of hibernating myocardium Eur. Heart J., February 2, 2007; 28(4): 499 - 509. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Bito, J. van der Velden, P. Claus, C. Dommke, A. Van Lommel, L. Mortelmans, E. Verbeken, B. Bijnens, G. Stienen, and K. R. Sipido Reduced Force Generating Capacity in Myocytes From Chronically Ischemic, Hibernating Myocardium Circ. Res., February 2, 2007; 100(2): 229 - 237. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Hamacher-Brady, N. R. Brady, and R. A. Gottlieb Enhancing Macroautophagy Protects against Ischemia/Reperfusion Injury in Cardiac Myocytes J. Biol. Chem., October 6, 2006; 281(40): 29776 - 29787. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. T. Krause, K. Jaquet, S. Geidel, C. Schneider, C. Mandel, H.-P. Stoll, K. Hertting, T. Harle, and K.-H. Kuck Percutaneous endocardial injection of erythropoietin: Assessment of cardioprotection by electromechanical mapping Eur J Heart Fail, August 1, 2006; 8(5): 443 - 450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zampino, M. Yuzhakova, J. Hansen, R. D. McKinney, P. H. Goldspink, D. L. Geenen, and P. M. Buttrick Sex-related dimorphic response of HIF-1{alpha} expression in myocardial ischemia Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H957 - H964. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Hasegawa, H. Takano, K. Iwanaga, M. Ohtsuka, Y. Qin, Y. Niitsuma, K. Ueda, T. Toyoda, H. Tadokoro, and I. Komuro Cardioprotective Effects of Granulocyte Colony-Stimulating Factor in Swine With Chronic Myocardial Ischemia J. Am. Coll. Cardiol., February 21, 2006; 47(4): 842 - 849. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Depre, L. Wang, X. Sui, H. Qiu, C. Hong, N. Hedhli, A. Ginion, A. Shah, M. Pelat, L. Bertrand, et al. H11 Kinase Prevents Myocardial Infarction by Preemptive Preconditioning of the Heart Circ. Res., February 3, 2006; 98(2): 280 - 288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J. Klocke Resting Blood Flow in Hypocontractile Myocardium: Resolving the Controversy Circulation, November 22, 2005; 112(21): 3222 - 3224. [Full Text] [PDF]
|
|
|
|
 |
|
 N. Hedhli, M. Pelat, and C. Depre Protein turnover in cardiac cell growth and survival Cardiovasc Res, November 1, 2005; 68(2): 186 - 196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Yan, D. E. Vatner, S.-J. Kim, H. Ge, M. Masurekar, W. H. Massover, G. Yang, Y. Matsui, J. Sadoshima, and S. F. Vatner Autophagy in chronically ischemic myocardium PNAS, September 27, 2005; 102(39): 13807 - 13812. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. T. Hua, H. Albadawi, F. Entabi, M. Conrad, M. C. Stoner, B. T. Meriam, R. Sroufe, S. Houser, G. M. LaMuraglia, and M. T. Watkins Polyadenosine Diphosphate-Ribose Polymerase Inhibition Modulates Skeletal Muscle Injury Following Ischemia Reperfusion Arch Surg, April 1, 2005; 140(4): 344 - 351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Heusch, R. Schulz, and S. H. Rahimtoola Myocardial hibernation: a delicate balance Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H984 - H999. [Abstract] [Full Text] [PDF]
|
|