© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
Targeted disruption of the protein kinase C epsilon gene abolishes the infarct size reduction that follows ischaemic preconditioning of isolated buffer-perfused mouse hearts
aDepartment of Cardiology, KCL, The Rayne Institute, St. Thomas’ Hospital, London SE1 7EH, UK
bImperial Cancer Research Fund, London, UK
cAcademic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
dInstitute of Child Health, Great Ormond Street Hospital, University College London, London WC1N 1EH, UK
* Corresponding author. Tel.: +44-171-922-8191; fax: +44-171-960-5659 adrian.saurin{at}kcl.ac.uk
Objective: Activation of protein kinase C (PKC) isoforms is associated with the cardioprotective effect of early ischaemic preconditioning (IP). PKC consists of at least 10 different isoforms, encoded by separate genes, which mediate distinct physiological functions. Although the PKC-
isoform has been implicated in preconditioning, uncertainty remains. We investigated whether preconditioning still occurs in a mouse line lacking cardiac PKC- protein due to a targeted disruption within the pkc- allele. Methods: The isolated buffer-perfused hearts from knockout mice lacking PKC- (–/–) and sibling heterozygous mice (+/–), with a normal PKC- complement, were preconditioned by 4x4 min ischaemia/6 min reperfusion. Hearts then underwent 45 min of global ischaemia followed by 1.5 h of reperfusion. Results: In PKC- (+/–) hearts ischaemic preconditioning reduced infarction volume as a percentage of myocardial volume (24.3±4.5 vs. 41.3±4.7%, P<0.001). In contrast, in PKC- (–/–) hearts preconditioning failed to diminish infarction (36.4±2.9 vs. 38.8±4.5%). Surprisingly however, although preconditioning did not reduce infarct size, it did enhance contractile recovery in PKC- (–/–) mice (43.1±3.9 vs. 24.9±5.1%, P<0.05), similar to the level seen in PKC- (+/–) hearts (35.2±3.9 vs. 20.9±5.0%, P<0.05). Conclusions: These data suggest that PKC- is essential for the reduction in infarction that follows early ischaemic preconditioning, but is not associated with the improvement in functional recovery.
KEYWORDS Preconditioning; Protein kinases; Ischemia
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|
|
|
|
|
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