Apr 1, 1996

Induction of tissue inhibitor of metalloproteinase and its mitogenic response to endothelial cells in human atherosclerotic and restenotic lesions

The Canadian Journal of Cardiology
S C TyagiD J Voelker


Expression of extracellular matrix (ECM), including collagens and proteoglycans, is increased following atherosclerosis and restenosis. To understand the Mechanism of ECM induction and accumulation, the balance among neutral matrix metalloproteinases (MMP), tissue inhibitor of metalloproteinase (TIMP) and activator (tissue plasminogen activator (tPA)) following atherosclerosis and restenosis was measured in human normal artery, and native atherosclerotic and restenotic lesions. Based on zymographic analysis, a correlation between the increase in latent and intrinsic MMP activity and an increase in the duration from first angioplasty to restenotic atherectomy was found, suggesting decreased MMP activity from normal tissue to restenotic tissue. ELISA was carried out to measure the level of TIMP. Inhibition of collagenase activity, against fluorescein-conjugated type I collagen degradation, by normal, de novo and restenotic extracts was determined. TIMP levels were found to be increased in restenotic lesions (0.38+/-0.04 ng/mL) compared with normal arterial tissue (0.27+/-0.05 ng/mL) and with tissue derived from de novo (0.30+/-0.02 ng/mL atherosclerotic lesions. Mitogenic activity of tissue extracts, against normal human heart en...Continue Reading

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Mentioned in this Paper

Coronary Restenosis
Extracellular Matrix
Enzyme Inhibitors

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