Salvianolic acid B inhibits SDF-1 alpha-stimulated cell proliferation and migration of vascular smooth muscle cells by suppressing CXCR4 receptor

Salvianolic acid B (Sal B), a bioactive compound from Salvia miltiorrhiza, widely used to treat cardiovascular diseases, and stromal cell-derived factor-1 alpha (SDF-1 alpha)/CXCR4 pathway has been correlated with balloon angioplasty-induced neointimal formation. The purposes of the present study were to investigate whether Sal B can inhibit SDF-1 alpha/CXCR4-mediated effects on the cell proliferation and migration of vascular smooth muscle cells (VSMCs) and to examine its possible molecular mechanisms. Under 0.5% FBS medium, all of the cellular studies were investigated on VSMCs (A10 cells) stimulated with 10 ng/ml SDF-1 alpha alone or co-treated with 0.075 mg/ml Sal B. Our results showed that SDF-1 alpha markedly stimulated the cell growth and migration of A10 cells, whose effects can be significantly reversed by co-incubation of Sal B. Similarly, Sal B also obviously down-regulated the SDF-1 alpha-stimulated up-regulation of CXCR4 (total and cell-surface levels), Raf-1, MEK, ERK1/2, phospho-ERK1/2, FAK and phospho-FAK as well as an increase of the promoter activity of NF-kappa B. Besides, Sal B also effectively attenuated balloon angioplasty-induced neointimal hyperplasia. In conclusion, suppressing the expression levels of CXCR4 receptor and downstream molecules of SDF-1 alpha(1/CXCR4 axis could possibly explain one of the pharmacological mechanisms of Sal B on prevention of cell proliferation, migration and subsequently neointimal hyperplasia. (C) 2011 Elsevier Inc. All rights reserved.