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Inhibition of matrix metalloproteinases by tissue factor pathway inhibitor-2

Tissue factor pathway inhibitor-2 reduces interstitial collagenase degradation of triple-helical collagen and may be of use in the treatment of atherosclerosis.

Tudor Toma(ttoma@mail.dntis.ro)

Matrix metalloproteinases (MMP) are involved in the degradation of extracellular collagen, which in vasculature promotes atheroma plaque rupture. Dysregulated MMP activity — probably due to an imbalance of endogenous inhibitors — could therefore be involved in the mechanisms of atherosclerosis. In the May Journal of Clinical Investigation Michael Herman and colleagues from Harvard Medical School, Boston report on the discovery of a new inhibitor of MMPs — the serine proteinase inhibitor tissue factor pathway inhibitor-2 (TFPI-2).

Despite its name, tissue factor pathway inhibitor-2 (TFPI-2) is a poor inhibitor of tissue factor (TF) and as yet has no defined physiologic function. Working on primary cells from human vasculature, Herman et al found that TFPI-2 diminished the ability of the interstitial collagenases MMP-1 and MMP-13 to degrade triple-helical collagen, the primary load-bearing molecule of the extracellular matrix within human atheroma. In addition, TFPI-2 also reduced the activity of the gelatinases MMP-2...

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