Vascular smooth muscle cell phenotypic modulation and the extracellular matrix

• Angioplasty disrupts vascular smooth muscle cell (VSMC) attachments to matrix proteins.
• This leads to the acquisition of a proliferative phenotype in VSMC.
• Excessive VSMC proliferation may lead to wall dysfunction and vessel disease.
• Matrix components may therefore have an important role in regulating restenosis.

Intervascular stents provide clinical benefits in preventing occlusive coronary artery disease after angioplasty, but intimal hyperplasia and restenosis after stent implantation remains an unresolved problem. Vascular smooth muscle cells (VSMCs), the main component of medial layer of arteries, play an important role in neointimal hyperplasia. After arterial injury, quiescent, contractile VSMCs undergo a change in phenotype; they proliferate and migrate from the media to the intima. It has been shown that the extracellular matrix (ECM) plays a key role in tissue formation, homeostasis and repair. The adhesion, proliferation, and migration of VSMCs are strongly influenced by interaction with ECM components including proteoglycans, glycoproteins such as fibronectin, collagen, elastic fibers (laminae). This interaction is further diversified under the influence of multiple transmembrane receptors and matrix proteinases. Hence, the coordinated regulation of VSMC function by these matrix components is an essential process for controlling the development and remodeling of the vascular system. Here the role of ECM in VSMC phenotypic modulation and neointimal hyperplasia will be reviewed.