Activation of calpain-1 in human carotid artery atherosclerotic lesions.
BACKGROUND
In a previous study, we observed that oxidized low-density lipoprotein-induced death of endothelial cells was calpain-1-dependent. The purpose of the present paper was to study the possible activation of calpain in human carotid plaques, and to compare calpain activity in the plaques from symptomatic patients with those obtained from patients without symptoms.


METHODS
Human atherosclerotic carotid plaques (n = 29, 12 associated with symptoms) were removed by endarterectomy. Calpain activity and apoptosis were detected by performing immunohistochemical analysis and TUNEL assay on human carotid plaque sections. An antibody specific for calpain-proteolyzed alpha-fodrin was used on western blots.


RESULTS
We found that calpain was activated in all the plaques and calpain activity colocalized with apoptotic cell death. Our observation of autoproteolytic cleavage of the 80 kDa subunit of calpain-1 provided further evidence for enzyme activity in the plaque samples. When calpain activity was quantified, we found that plaques from symptomatic patients displayed significantly lower calpain activity compared with asymptomatic plaques.


CONCLUSIONS
These novel results suggest that calpain-1 is commonly active in carotid artery atherosclerotic plaques, and that calpain activity is colocalized with cell death and inversely associated with symptoms.
Gonçalves
Isabel
I
Department of Laboratory Medicine/Experimental Pathology, Lund University, Malmö, Sweden. isabel.goncalves@med.lu.se
Nitulescu
Mihaela
M
Saido
Takaomi C
TC
Dias
Nuno
N
Pedro
Luis M
LM
E Fernandes
José Fernandes
JF
Ares
Mikko P S
MP
Pörn-Ares
Isabella
I
D000368:Aged; D017209:Apoptosis; D002154:Calpain / Q000378:metabolism*; D002339:Carotid Arteries / Q000201:enzymology* / Q000473:pathology; D016893:Carotid Stenosis / Q000201:enzymology* / Q000473:pathology; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
D002154:Calpain