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Abstract
Background. Matrix metalloproteinase enzymes (MMP) have been identified in carotid atherosclerotic
plaques, but their role in the development of clinical symptoms remains ill defined.
We correlated the activity and levels of metalloproteinase enzymes and their inhibitors
in human carotid plaques to ischemic neurologic events.
Methods. Carotid plaques were collected at the time of endarterectomy from 23 patients with
carotid stenosis. Sixteen patients were asymptomatic and 7 patients had symptoms of
stroke or transient ischemic attack within 6 weeks of surgery. Protein was extracted
from the plaques, proteolytic activity was determined by gelatin zymography, and pro-MMP
and tissue inhibitor of metalloproteinase (TIMP) enzyme content were measured by ELISA
assay. Macrophage accumulation in the plaque was determined using immunohistochemistry.
Results. Plaques from symptomatic patients had decreased proteolytic activity on substrate
gel zymography at the 62- and 92-kDa regions (corresponding to active MMP-2 and pro-MMP-9).
A decrease in pro-MMP-9 (8.21 ± 2.35 vs 17.42 ± 3.14 ng, P < 0.05) and an increase in TIMP-2 protein (12.62 ± 0.58 vs 10.56 ± 0.77 ng, P < 0.05) were noted on ELISA in plaques from symptomatic patients. No difference was
noted in macrophage accumulation in the plaques between the two groups.
Conclusions. Plaques from patients who present with ischemic neurologic symptoms have decreased
proteolytic activity associated with decreased pro-MMP-9 and increased TIMP-2 protein
levels. These data suggest that metalloproteinase enzymes are not responsible for
plaque instability in the carotid circulation and may in fact promote plaque stability.
Keywords
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References
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Article info
Footnotes
☆Supported in part by Beginning Grant-In-Aid 96-GB-53 from the American Heart Association, Wisconsin Affiliate.
☆☆Presented at the 23rd Annual Symposium of the Association of Veterans Administration Surgeons, St. Louis, MO, May 2–4, 1999.
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Copyright
© 2000 Academic Press. Published by Elsevier Inc. All rights reserved.
