Copyright © 2006, European Society of Cardiology
The end-effectors of preconditioning protection against myocardial cell death secondary to ischemia–reperfusion
Servicio de Cardiologia, Hospital Universitari Vall d–Hebron, Passeig Vall d–Hebron, 119-129, 08035 Barcelona, Spain
* Corresponding author. Tel.: +34 93 4894038; fax:+ 34 93 4894032. Email address: dgdorado{at}vhebron.net
Our understanding of the end-effectors involved in preconditioning protection is still very limited. This is partially due to an incomplete knowledge of the mechanisms responsible for acute sarcolemmal rupture and cell death during the first minutes of reperfusion, including the relative roles of hypercontracture-mediated sarcolemmal rupture and mitochondrial permeability transition pore (MPTP) opening-mediated cell death. In the present article, the role of proposed end-effectors of preconditioning protection, defined as molecules directly involved in cell death that are modified by ischemic preconditioning (IP), is examined. IP attenuates hypercontracture-mediated cell death, probably through several mechanisms, including attenuated calpain activation during reperfusion leading to preserved cytoskeletal integrity and accelerated recovery of Na+/K+-ATPase function, but probably also protein kinase G (PKG)-mediated improved calcium handling. The potential role of gap junctions in preconditioning protection is controversial, but the recently discovered mitochondrial localisation of connexin43 seems to play an important role in protection that has not yet been completely defined. Several recent studies suggest that IP can reduce MPTP opening during reperfusion and limit infarct size through this mechanism, although the contribution of this widely accepted mechanism to the infarct size reduction induced by IP in the intact heart needs to be established.
KEYWORDS Myocardial infarction; Hypercontracture; Calpain; Connexin43; cGMP; PKG; Mitochondrial permeability transition; GSK3beta
Time for primary review 30 days
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. R. Sipido, A. Tedgui, S. D. Kristensen, G. Pasterkamp, H. Schunkert, M. Wehling, P. G. Steg, W. Eisert, F. Rademakers, B. Casadei, et al. Identifying needs and opportunities for advancing translational research in cardiovascular disease Cardiovasc Res, August 1, 2009; 83(3): 425 - 435. [Full Text] [PDF]
|
|
|
|
|
|
K. Boengler, R. Schulz, and G. Heusch Loss of cardioprotection with ageing Cardiovasc Res, July 15, 2009; 83(2): 247 - 261. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kato, M. Akao, M. Matsumoto-Ida, T. Makiyama, M. Iguchi, T. Takeda, S. Shimizu, and T. Kita The targeting of cyclophilin D by RNAi as a novel cardioprotective therapy: evidence from two-photon imaging Cardiovasc Res, July 15, 2009; 83(2): 335 - 344. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Nadtochiy, P. R.S. Baker, B. A. Freeman, and P. S. Brookes Mitochondrial nitroalkene formation and mild uncoupling in ischaemic preconditioning: implications for cardioprotection Cardiovasc Res, May 1, 2009; 82(2): 333 - 340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ruiz-Meana, A. Rodriguez-Sinovas, A. Cabestrero, K. Boengler, G. Heusch, and D. Garcia-Dorado Mitochondrial connexin43 as a new player in the pathophysiology of myocardial ischaemia-reperfusion injury Cardiovasc Res, January 15, 2008; 77(2): 325 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Inserte Triggering of cardiac preconditioning through Na+/K+-ATPase Cardiovasc Res, February 1, 2007; 73(3): 446 - 447. [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. Halestrap Mitochondria and Preconditioning: A Connexin Connection? Circ. Res., July 7, 2006; 99(1): 10 - 12. [Full Text] [PDF]
|
|
|
|
|
|
D. Garcia-Dorado, J. Vinten-Johansen, and H. M. Piper Bringing preconditioning and postconditioning into focus Cardiovasc Res, May 1, 2006; 70(2): 167 - 169. [Full Text] [PDF]
|
|