Increased matrix metalloproteinase-9 activity in unstable carotid plaques. A potential role in acute plaque disruption.
OBJECTIVE
Acute disruption of atherosclerotic plaques precedes the onset of clinical syndromes, and studies have implicated a role for matrix metalloproteinases (MMPs) in this process. The aim of this study was to establish the character, level, and expression of MMPs in carotid plaques and to correlate this with clinical status, cerebral embolization, and histology.


METHODS
Plaques were obtained from 75 consecutive patients undergoing carotid endarterectomy and divided into 4 groups according to symptomatology (group 1, asymptomatic; group 2, symptomatic >6 months before surgery; group 3, symptomatic within 1 to 6 months; group 4, symptomatic within 1 month). All patients underwent preoperative and intraoperative transcranial Doppler monitoring. Plaques were subjected to histological examination and quantification of MMPs by zymography and ELISA.


RESULTS
The level of MMP-9 was significantly higher in group 4 (median 125.7 ng/mL for group 4, median <32 ng/mL for all other groups; P=0.003), with no difference in the levels of MMPs 1, 2, or 3. Furthermore, the MMP-9 concentration was significantly higher in plaques undergoing spontaneous embolization (P=0.019) and those with histological evidence of plaque instability (P<0.03). In situ hybridization demonstrated increased MMP-9 expression in highly symptomatic plaques in areas of intense inflammatory infiltrate.


CONCLUSIONS
The concentration, production, and expression of MMP-9 is significantly higher in unstable carotid plaques. If this proves to be a causal relationship, MMP-9 may be a strong candidate for pharmacotherapy aimed at stabilizing plaques and preventing stroke.
Loftus
I M
IM
University Department of Surgery, Leicester Royal Infirmary, Leicester, UK. ianloftus@aol.com
Naylor
A R
AR
Goodall
S
S
Crowther
M
M
Jones
L
L
Bell
P R
PR
Thompson
M M
MM
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D002340:Carotid Artery Diseases / Q000201:enzymology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D008875:Middle Aged; D011237:Predictive Value of Tests; D012422:Rupture, Spontaneous
D015415:Biomarkers; D020780:Matrix Metalloproteinase 9