Integrin α 7 β 1 COMPels Smooth Muscle Cells to Maintain Their Quiescence

Abstract

See related articles, pages 514–525 Arterial smooth muscle cells (SMCs) normally reside in the arterial wall in a differentiated contractile state. Following injury, such as that caused by angioplasty or stenting, or in more chronic conditions, such as atherosclerosis, some SMCs in the arterial wall convert to a less differentiated state, often termed dedifferentiated, synthetic, or proliferative state.1 These dedifferentiated or synthetic SMCs gain the ability to respond to growth factors, and to migrate and proliferate. At the same time, they lose several cytoskeletal markers of differentiation and most likely their ability to respond to contractile stimuli and to contribute to vessel contraction. It has long been known that there is an inverse correlation between SMC proliferation and their expression of cytoskeletal markers of differentiation.2 Understanding of the factors regulating SMC differentiation is important, because maintaining SMC differentiation in conditions normally associated with increased SMC dedifferentiation would presumably prevent restenosis following angioplasty and development of irreversible atherosclerotic lesions characterized by SMC proliferation and migration. What are the extracellular cues that determine the differentiation state of SMCs? It has been known for decades that the extracellular matrix (ECM) surrounding SMCs is one important factor, and perhaps the principal factor, for maintaining SMCs in a differentiated state. Thus, SMCs isolated from the arterial wall and plated onto laminin or type IV collagen retain their differentiated phenotype to a greater extent than do SMCs plated onto fibronectin or monomeric type I collagen.3–4 Interestingly, the ECM surrounding the SMC not only regulates the differentiation state of the SMC but also determines whether the cell is able to respond to the action of growth factors, such as platelet-derived growth factor (PDGF). In addition, the 3D structure of the ECM …