Vascular Cell Locomotion

Abstract

See related article, pages 1479–1489 Since the discovery of osteopontin (OPN) in the vasculature, vascular biologists have been intrigued by its potential role in vascular arteriosclerosis and vessel calcification during the aging process.1 Osteopontin is a phosphorylated acidic glycoprotein adhesion molecule, originally cloned from bone; and as in bone, its cardiovascular functions include cellular migration, adhesion, and spreading.2 The most salient features of this intriguing calcium-regulating molecule are its ability to interact with αvβ3 and other integrins on the surface of cells. Because this ligand–receptor complex is known to be involved in cell migration, it is not surprising that an antibody to the β3 subunit of this receptor effectively reduced restenosis in patients.3 Interestingly, angiotensin II and other growth factors, including platelet-derived growth factor and transforming growth factor-β, regulate OPN gene expression in vascular smooth muscle cell (VSMC) cultures and fibroblasts.1,4 Cardiac fibroblasts have been extensively reported to produce OPN in response to these growth factors, resulting in fibroblast proliferation. On the one hand, OPN is thought to cause vascular dystrophy by altering extracellular matrix formation; on the other hand, cellular motogenesis is a hallmark of this emerging vascular cytokine. Its cellular expression includes a variety of inflammatory cells, such as T cells and macrophages, as well as mesenchymal cells of the vasculature including adventitial myofibroblasts. Moreover, OPN has both pro- and antiinflammatory properties. As a proinflammatory agent it can attract and modulate the function of the above mentioned cell types. Of seemingly major importance, OPN interacts with intracellular signaling agents to promote cell migration and matrix metalloproteinases, both of which are required for cell tunneling through dense and elastin-rich vascular tissue. In fibroblasts these agents appear to include cell surface CD44 and ERM proteins located just below the plasma membrane …