Immunohistochemical expression of activated caspase-3 in human myocardial infarction.
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.
Zidar
Nina
N
Institute of Pathology, Medical Faculty, University of Ljubljana, Korytkova 2, 1000 Ljubljana, Slovenia. nina.zidar@mf.uni-lj.si
Dolenc-Strazar
Zvezdana
Z
Jeruc
Jera
J
Stajer
Dusan
D
D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis*; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D015425:Myocardial Reperfusion; D009504:Neutrophils / Q000378:metabolism; D013997:Time Factors
C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases