Matrix Metalloproteinase (MMP)-3 Activates MMP-9 Mediated Vascular Smooth Muscle Cell Migration and Neointima Formation in Mice

OBJECTIVE—Several matrix metalloproteinases (MMPs) have been implicated in extracellular matrix destruction and other actions that lead to plaque rupture and myocardial infarction. Conversely, other MMPs have been shown to promote vascular smooth muscle cell (VSMC)–driven neointima formation, which contributes to restenosis, fibrous cap formation, and plaque stability. MMP-3 knockout reduced VSMC accumulation in mouse atherosclerotic plaques, implicating MMP-3 in neointima formation. We therefore investigated the effect of MMP-3 knockout on neointima formation after carotid ligation in vivo and VSMC migration in vitro. METHODS AND RESULTS—Twenty-eight days after left carotid ligation, MMP-3 knockout significantly reduced neointima formation (75%, P