Role of alpha 5 beta 1 and alpha v beta 3 integrins on smooth muscle cell spreading and migration in fibrin gels

Fibrin is found at sites of vascular injury and is one of the major matrix ligands for beta 3 integrins, Blocking the beta 3 integrin on smooth muscle cell is hypothesized as a potential target to prevent restenosis because i t could inhibit cell attachment and migration into fibrin provisional matri x. Human aortic smooth muscle cells (HNB18E6E7) spread stably in plasma gel s within 24 h. Cell spreading was dramatically blocked by simultaneous use of alpha 5 beta 1 and alpha v beta 3 integrin antibodies (P <0.0001), howev er, blocking of either integrin alone failed to inhibit spreading. GPenGRGD SPCA, which has been considered a specific alpha v beta 3 antagonist, inhib ited spreading at 500 mu M, suggesting that the peptide blocked both alpha 5 beta 1 and alpha v beta 3, Similarly, invasive migration into fibrin gels was blocked by simultaneous use of both alpha 5 beta 1 and alpha v beta 3 antibodies, however, blocking of either integrin alone failed to effect cel l migration. Another migration assay using transwell indicated similar resu lts. In conclusion, both alpha 5 beta 1 and alpha v beta 3 integrins are re sponsible for smooth muscle cell spreading and migration into fibrin gels. These data suggest that blocking beta 3 integrin alone would not affect smo oth muscle cell interaction with fibrin.