Expression of matrix metalloproteinases and their inhibitor TIMP-1 in the rat carotid artery after balloon injury.
ARTERIOSCL THROM VAS
1837 - 1844.
The temporal relationship of matrix metalloproteinases (MMPs) and a specific tissue inhibitor (TIMP-1) has been examined by reverse transcription-polymerase chain reaction and substrate zymography, after balloon catheter angioplasty of the rat carotid artery. The contralateral uninjured carotid artery was used as a comparative control. Of the MMPs examined, only MMP-2 (72-kDa gelatinase) was produced constitutively by normal uninjured arteries. After injury, MMP-2 mRNA levels fell compared with the uninjured arteries; by 24 hours, levels had increased 2-fold. Zymography showed that the inactive form of MMP-2 predominated in uninjured vessels, but after injury, the level of the active form was increased. MMP-9 (92-kDa gelatinase) mRNA levels and activity peaked at 6 hours after injury and were still detectable al 7 days. MMP-3 (stromelysin) expression was detectable at low levels as early as 2 hours after injury and showed an approximate 2-fold increase of expression at 7 days. The presence of the active protein paralleled the mRNA expression. The inhibitor TIMP-1 mRNA was first detected 6 hours after injury and showed a marked peak of expression at 24 hours; however, no expression was detected by 7 days. The presence of a constitutively expressed, low molecular weight caseinolytic enzyme (27 kDa) was observed, and the induction of a caseinolytic enzyme (30 kDa) was noted that was induced as early as 2 hours after injury, peaked at 6 hours, and was barely detectable by 7 days. These results demonstrate that the process of extracellular matrix breakdown by MMPs after balloon catheter-induced injury is controlled by a tightly regulated temporal response by the genes responsible for the production of these enzymes and their inhibitor and by posttranslational activation of the proenzymes.
|Title:||Expression of matrix metalloproteinases and their inhibitor TIMP-1 in the rat carotid artery after balloon injury|
|Keywords:||matrix metalloproteinases, RT-PCR, rat, carotid artery, injury, MUSCLE-CELL-PROLIFERATION, POLYMERASE CHAIN-REACTION, HUMAN SYNOVIAL-CELLS, GENE-EXPRESSION, ATHEROSCLEROTIC PLAQUES, TISSUE INHIBITOR, MESSENGER-RNA, HUMAN-SKIN, DEGRADING METALLOPROTEINASES, INTERSTITIAL COLLAGENASE|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of) > Metabolism and Experimental Therapeutics
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
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