Move On!

Abstract

See related article, pages 817–825 A cardinal feature of the response to injury within the muscularized, adult blood vessel wall is the transformation of an highly organized, isometric, cytoskeletal archetype, housed within vascular smooth muscle cells (SMCs), to one that supports cell migration, the function of which is to elicit repair.1 Such reorganization of the SMC cytoskeleton permits cells to move from the comfort of their controlled environment, which includes the surrounding extracellular matrix (ECM) and their neighboring cells, to the site of injury. Cytoskeletal remodeling also initiates other functions required for the injury-repair response, including SMC proliferation, and the creation of a provisional ECM that supports cell motility, growth and survival.2,3 For the most part, these and many other repair-related processes, including the recruitment and differentiation of inflammatory and stem cells to sites of injury,4,5 are coordinated through changes in cell-cell and cell–matrix adhesion, which collectively act with numerous other intrinsic and extrinsic factors, to stimulate or repress programs of signal transduction and gene expression. Sometimes, however, overexuberant responses to injury lead to hyper-repair of blood vessels, leaving them occluded and functionless.1,6 Thus, identifying molecules and pathways that control cytoskeletal homeostasis and remodeling represents a critical step in comprehending how blood vessels develop, and how SMCs contained therein adapt to injury in the fetal-, neo-, and postnatal periods. With respect to the general cellular mechanisms leading to increased SMC motility, reorganization of the cytoskeleton relies on the recruitment of multiple signaling and adaptor proteins to focal or fibrillar adhesion sites that reiteratively form, deconstruct and regenerate themselves, allowing cells to detach and reattach to the existing and provisional matrix on which they exert a tractional force.7 In essence, adhesion sites not only contain solid-state, cytoskeleton-enriched scaffolds that transmit force from the outside of …