alpha v beta 3, alpha v beta 5, and osteopontin are coordinately upregulated at early time points in a rabbit model of neointima formation

Both smooth muscle cell migration and replication are known to be responsib le for neointima formation. Recent reports based on in vitro studies and an imal models of neointima formation highlight the possible importance of alp ha v beta 3 and alpha v beta 5 integrins in mediating neointima formation. Clinical data suggest that specific alpha v beta 3 blockade may limit reste nosis. The aim of this study was to identify the expression of alpha v beta 3 and alpha v beta 5 and their ligand osteopontin in the very early phases of neointima formation in a rabbit model. A non-occlusive cuff placed arou nd the rabbit femoral artery resulted in a complete, concentric neointima t hat formed by 14 days. Antibodies specific for the integrin heterodimers an d for osteopontin, along with a probe specific for osteopontin mRNA, were u sed to identify expression at early time paints (6 h, 1 day, 3 days, 5 days ) post-cuffing. Immunohistochemistry and in situ hybridization expression r esults were quantitated by image analysis and tested for statistical signif icance by a two-tailed t-test. The data demonstrated the rapid (within 6 h) and abundant upregulation of alpha v beta 3 and alpha v beta 5 integrins a nd their ligand during very early time points of neointima formation. The v ery early (6 h) upregulation of alpha v beta 3 underscores a potentially im portant clinical intervention point in limiting restenosis following clinic al angioplasty procedures. I. Cell. Biochem. 75:492-504, 1999. (C) 1999 Wil ey-Liss, Inc.