Matrix metalloproteinases regulate migration, proliferation, and death of vascular smooth muscle cells by degrading matrix and non-matrix substrates

Intimal thickening occurs in blood vessels in response to injury or atherosclerosis. The balance of migration and proliferation of vascular smooth muscle cells (VSMC) over death by apoptosis has an important impact on the final size of intimal thickening and may also affect atherosclerotic plaque stability. All aspects of VSMC behaviour are under coordinated control by growth factors, cell–matrix and cell–cell interactions. We review the evidence that matrix-degrading metalloproteinases (MMPs) regulate migration, proliferation and survival of VSMC. Moreover, we discuss critically the underlying mechanisms, which include changing growth factor availability and remodelling cell–matrix and cell–cell contacts. We conclude that MMPs influence VSMC behaviour by cleaving both matrix and non-matrix substrates.