Document Detail

Role of matrix metalloproteinase-2 in the cardioprotective effect of ischaemic postconditioning.
MedLine Citation:
PMID:  19880538     Owner:  NLM     Status:  MEDLINE    
The activation of matrix metalloproteinases (MMPs) contributes to myocardial injury at the onset of reperfusion; however, their role in ischaemic postconditioning is unknown. The aim of the present study was to examine the effects of ischaemic postconditioning on MMP activity in isolated rabbit hearts. The isolated rabbit hearts were subjected to 30 min of global ischaemia followed by 180 min of reperfusion (I/R group; n = 8). In the ischaemic postconditioning group (n = 8), a postconditioning protocol was performed (2 cycles of 30 s reperfusion-ischaemia). In other experiments, we added doxycycline, an MMP inhibitor, at 25 (n = 7) or 50 micromol l(1) (n = 8) during the first 2 min of reperfusion. Coronary effluent and left ventricular tissue were collected during pre-ischaemic conditions and at different times during the reperfusion period to measure MMP-2 activity and cardiac protein nitration. We evaluated ventricular function and infarct size. In the I/R group, infarct size was 32.1 +/- 5.2%; Postcon reduced infarct size to 9.5 +/- 3.8% (P < 0.05) and inhibited MMP-2 activity during reperfusion. The administration of doxycycline at 50 micromol l(1) inhibited MMP-2 activity and cardiac protein nitration and reduced the infarct size to 9.7 +/- 2.8% (P < 0.05). A lower dose of doxycycline (25 micromol l(1)) failed to inhibit MMP-2 activity and did not modify the infarct size. Our results strongly suggest that ischaemic postconditioning may exert part of its cardioprotective effects through the inhibition of MMP-2 activity.
Mart?n Donato; Ver?nica D'Annunzio; Bruno Buchholz; Ver?nica Miksztowicz; Cristina Lorenzo Carri?n; Laura B Valdez; Tamara Zaobornyj; Laura Schreier; Regina Wikinski; Alberto Boveris; Gabriela Berg; Ricardo J Gelpi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-10-30
Journal Detail:
Title:  Experimental physiology     Volume:  95     ISSN:  1469-445X     ISO Abbreviation:  Exp. Physiol.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-12     Completed Date:  2010-05-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9002940     Medline TA:  Exp Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  274-81     Citation Subset:  IM    
Institute of Cardiovascular Physiopathology, Department of Pathology, University of Buenos Aires, JE Uriburu 950, 2nd floor, C1114AAD, Buenos Aires, Argentina.
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MeSH Terms
Coronary Circulation
Enzyme Activation
Heart Ventricles / physiopathology*
Matrix Metalloproteinase 2 / metabolism*
Myocardial Reperfusion Injury / complications,  physiopathology*
Ventricular Dysfunction, Left / etiology,  physiopathology*
Reg. No./Substance:
EC Metalloproteinase 2

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