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(

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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