Differences in matrix metalloproteinase-1 and matrix metalloproteinase-12 transcript levels among carotid atherosclerotic plaques with different histopathological characteristics.
OBJECTIVE
Previous studies have shown that atherosclerotic lesions express a number of matrix metalloproteinases (MMPs). Here we investigated whether transcript levels of MMP-1, -3, -7, -9, and -12 in carotid atherosclerotic plaques were correlated with histological features and clinical manifestations.


METHODS
Atherosclerotic plaques (n=50) removed from patients undergoing carotid endarterectomy were classified histologically using a system proposed by Virmani et al, and MMP-1, -3, -7, -9, and -12 transcript levels in these tissues were quantified by real-time reverse-transcriptase polymerase chain reaction.


RESULTS
Compared to plaques with a thick fibrous cap, those with a thin cap had a 7.8-fold higher MMP-1 transcript level (P=0.006). MMP-3, -7, and -12 were 1.5-fold, 1.8-fold, and 2.1-fold, respectively, higher in thin cap plaques, but the differences did not reach statistical significance. MMP-12 transcript levels were significantly increased in ruptured plaques compared with lesions without cap disruption (P=0.001). MMP-9 transcript levels were similar among the different types of lesion. MMP-1 and -12 transcript levels were significantly higher in plaques from patients with amaurosis fugax, than in those from asymptomatic patients (P=0.029 and P=0.008 for MMP-1 and MMP-12, respectively), than in those from patients with stroke (P=0.027 and P=0.001, respectively), and than in those from patients with transient ischemic attack (P=0.046 and P=0.008, respectively).


CONCLUSIONS
These data support a role of MMP-1 and -12 in determining atherosclerotic plaque stability.
Morgan
Angharad R
AR
Human Genetics Division, School of Medicine, University of Southampton, UK.
Rerkasem
Kittipan
K
Gallagher
Patrick J
PJ
Zhang
Baiping
B
Morris
Gareth E
GE
Calder
Philip C
PC
Grimble
Robert F
RF
Eriksson
Per
P
McPheat
William L
WL
Shearman
Clifford P
CP
Ye
Shu
S
D000368:Aged; D002340:Carotid Artery Diseases / Q000175:diagnosis* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis* / Q000235:genetics; D053508:Matrix Metalloproteinase 12; D008666:Metalloendopeptidases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism
D012333:RNA, Messenger; D008666:Metalloendopeptidases; C507122:MMP12 protein, human; D053508:Matrix Metalloproteinase 12; D020781:Matrix Metalloproteinase 1