Tissue inhibitors of metalloproteinases and metalloproteinases in atherosclerosis.

The ability of the metalloproteinases to degrade extracellular matrix proteins is essential for the matrix remodelling that occurs during infiltration of inflammatory cells, intimal thickening, angiogenesis and plaque rupture which are a result of atherosclerosis. Increased metalloproteinase activity therefore requires stimulation of metalloproteinase expression by cytokines and growth factors, activation of metalloproteinases, and downregulation of tissue inhibitors of metalloproteinases. In addition, metalloproteinases may influence atherosclerosis by processing of proteins involved in inflammation and cell growth and death and the tissue inhibitors of metalloproteinases may also play a less inhibitory role by influencing cell growth and apoptosis.