doi: 10.1161/01.RES.0000245431.16226.c6
© 2006 American Heart Association, Inc.
Editorials |
Preconditioning Enters the Era of "Physiological Proteomics"
From the Vascular Biology Unit (R.A.C.), Whitaker Cardiovascular Institute, BU NIH-NHLBI Cardiovascular Proteomics Center (R.A.C., M.E.M.), Mass Spectrometry Resource Center (M.E.M.), Boston University School of Medicine, Boston, Mass.
Correspondence to Richard A. Cohen, Vascular Biology Unit, Boston University School of Medicine, 650 Albany St, X720, Boston, MA 02118. E-mail racohen@bu.edu
See related article, pages 706–714
Key Words: preconditioning • proteomics • ischemia • mitochondria • mass spectrometry
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Cardiac ischemic preconditioning was first described in 1986 by Murry et al,1 who reported that brief periods of ischemia dramatically reduced myocardial infarct size caused by a subsequent, more prolonged period of ischemia. Since the initial report, the phenomenon has been shown to occur in many cell types, including human cardiomyocytes,2 raising hopes that ischemic injury to human myocardium might be prevented. The discovery that pretreatment with several pharmacological agents including adenosine, diazoxide, bradykinin, and insulin could also precondition the heart and prevent subsequent ischemic damage, provided an as yet unfulfilled promise that drugs could be developed which limit cardiac cell death caused by myocardial infarction in patients.3
As is always true of complex physiological problems, it is likely that understanding the fundamental molecular mechanism of preconditioning will be necessary to develop effective medical therapies. In recent years the mitochondrion has become the subject of intense scrutiny for the key to preconditioning. The formation of the mitochondrial permeability transition pore (mPTP) is an essential step in ischemia-induced cardiomyocyte death because its formation accounts for collapse of the mitochondrial membrane potential and failure of oxidative phosphorylation to produce ATP which leads to cardiomyocyte death. Furthermore, inhibitors and activators of the mPTP inhibit or favor preconditioning, respectively, suggesting both the mPTP and the mitochondrion are key participants.3,4
Further evidence that the mitochondrion is key to the initial physiological response to preconditioning is provided by Arrell et al in this issue of Circulation Research, who used a proteomic approach to measure changes
Related Article:
Circ. Res. 2006 99: 706-714.