Triflavin, an α_IIβ₃ disintegrin, inhibits cell adhesion and protein kinase C-α translocation in vascular smooth muscle cells

Abstract

Vascular smooth muscle cell (VSMC) adhesion and migration play important roles in atherosclerosis and intimal hyperplasia. In our previous study, we found that triflavin, a nonspecific Arg-Gly-Asp (RGD)-containing peptide (also named α_IIβ₃ disintegrin), may have dual beneficial effects in preventing neointimal formation by acting on both platelets and VSMCs, which has created new incentives for the development of drugs with this combined action. In the present study, triflavin (10, 20, and 50 μg/mL) concentration- dependently inhibited VSMC adhesion to immobilized fibronectin (50 μg/mL). In the flow cytometric study, we found that FITC–triflavin (5 μg/mL) bound directly to VSMC membranes. In a confocal microscopic study, fibronectin (50 μg/mL) markedly stimulated protein kinase C (PKC)-α translocation from the cytosol to the membranes, which was abolished in the presence of triflavin (10 μg/mL). In conclusion, the most important findings of this study suggest that triflavin, an α_IIβ₃ disintegrin, inhibited immobilized fibronectin-induced cell adhesion and PKC-α translocation in VSMCs.

Keywords::

• Vascular smooth muscle cell
• fibronectin
• PKC-α
• triflavin

Acknowledgements

This work was supported by a grant from the National Science Council of Taiwan (NSC 94-2321-B-038-001) and one from the Taipei Medical University–Mackay Memorial Hospital (94 MMH-TMU-05). The first two authors (C.-J.W. and C.-Y.H) contributed equally to this work. The authors alone are responsible for the content and writing of the paper.