Document Detail


Immunohistochemical expression of activated caspase-3 in human myocardial infarction.
MedLine Citation:
PMID:  16205944     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
There is mounting evidence that apoptosis is important in the pathogenesis of myocardial infarction (MI). One of the key events in the process of apoptosis is activation of caspase-3. Much attention has been recently paid to caspase inhibition as a potential treatment for ischemic cardiac disease. To predict the long-term effect of such treatment, it is essential to understand the significance of caspase-3 in the evolution of MI. Our aim was therefore to analyze immunohistochemical expression of activated caspase-3 in MI. Our study included autopsy samples of infarcted heart tissue from 50 patients with MI. Immunohistochemistry was performed by a sensitive peroxidase-streptavidin method on formalin-fixed, paraffin-embedded tissue, using monoclonal antibodies against activated (cleaved) caspase-3. We found caspase-3-positive myocytes in 18 MI less than 24 h old and in 3 MI that were presumably 48 h old. Their density (number of labeled myocytes/mm(2)) was greater in patients who received reperfusion treatment (mean 0.160+/-0.373 vs 0.025+/-0.037, p=0.06). In MI older than 48 h, positive reaction was observed in neutrophil granulocytes in the interstitium and, in subacute MI, it was observed in mononuclear inflammatory cells, myofibroblasts, and vascular endothelial cells. Our results suggest that apoptosis of myocytes is an important mode of cell death in the early MI, being enhanced in patients who received reperfusion treatment. After 48 h, apoptosis is an important mechanism of the clearance of neutrophil granulocytes and other inflammatory cells and of scar formation. Treatment with caspase inhibitors therefore will not only affect myocyte loss but will also interfere with the clearance of neutrophils and with the transformation of granulation tissue into a scar.
Authors:
Nina Zidar; Zvezdana Dolenc-Strazar; Jera Jeruc; Dusan Stajer
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Publication Detail:
Type:  Journal Article     Date:  2005-10-05
Journal Detail:
Title:  Virchows Archiv : an international journal of pathology     Volume:  448     ISSN:  0945-6317     ISO Abbreviation:  Virchows Arch.     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2006-02-01     Completed Date:  2006-10-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9423843     Medline TA:  Virchows Arch     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  75-9     Citation Subset:  IM    
Affiliation:
Institute of Pathology, Medical Faculty, University of Ljubljana, Korytkova 2, 1000 Ljubljana, Slovenia. nina.zidar@mf.uni-lj.si
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MeSH Terms
Descriptor/Qualifier:
Aged
Aged, 80 and over
Apoptosis / physiology
Caspase 3
Caspases / biosynthesis*
Enzyme Activation / physiology
Female
Humans
Image Processing, Computer-Assisted
Immunohistochemistry
Male
Middle Aged
Myocardial Infarction / metabolism*,  pathology*,  therapy
Myocardial Reperfusion
Neutrophils / metabolism
Time Factors
Chemical
Reg. No./Substance:
EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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