Vascular Smooth Muscle Cell Matrix-Degradation by Podosomes

Abstract

During plaque formation, vascular smooth muscle cells migrate from the medial layer into the intima. The exact mechanism by which vascular smooth muscle cells (VSMCs) invade through the extracellular matrix into the intimal layer remains unclear. VSMCs have been shown to exhibit podosomes, sub-cellular structures known to release matrix metalloproteinases. Here, we investigated the formation and matrix degrading ability of podosomes in VSMCs before and after treatment with phorbol 12, 13-dibutyrate (PDBu), an activator of protein kinase C (PKC). Using a fluorescently-labeled gelatin substrate, we find that VSMC degrade matrix even in the absence of observable podosome formation. However, the extent of degradation is significantly increased when podosome formation is induced using PDBu. Our current work is expanding these studies to identify the physical triggers of podosome formation in the in vivo microenvironment.