Role of α5β1 and αvβ3 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 it could inhibit cell attachment and migration into fibrin provisional matrix. Human aortic smooth muscle cells (HNB18E6E7) spread stably in plasma gels 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), however, blocking of either integrin alone failed to inhibit spreading. GPenGRGDSPCA, which has been considered a specific alpha v beta 3 antagonist, inhibited 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 cell migration. Another migration assay using transwell indicated similar results. In conclusion, both alpha 5 beta 1 and alpha v beta 3 integrins are responsible for smooth muscle cell spreading and migration into fibrin gels. These data suggest that blocking beta 3 integrin alone would not affect smooth muscle cell interaction with fibrin.