title: Salvianolic acid B inhibits SDF-1α-stimulated cell proliferation and migration of vascular smooth muscle cells by suppressing CXCR4 receptor.
abstract: Salvianolic acid B (Sal B), a bioactive compound from Salvia miltiorrhiza, widely used to treat cardiovascular diseases, and stromal cell-derived factor-1α (SDF-1α)/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-1α/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-1α alone or co-treated with 0.075 mg/ml Sal B. Our results showed that SDF-1α 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-1α-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-κB. 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-1α/CXCR4 axis could possibly explain one of the pharmacological mechanisms of Sal B on prevention of cell proliferation, migration and subsequently neointimal hyperplasia.
authors.affiliation: School of Pharmacy, China Medical University, Taichung 40402, Taiwan.
authors.forename: Chun-Hsu
authors.initials: CH
authors.lastname: Pan
authors.forename: Ching-Wen
authors.initials: CW
authors.lastname: Chen
authors.forename: Ming-Jyh
authors.initials: MJ
authors.lastname: Sheu
authors.forename: Chieh-Hsi
authors.initials: CH
authors.lastname: Wu
mesh_terms: D000800:Angioplasty, Balloon / Q000009:adverse effects; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006965:Hyperplasia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D058426:Neointima / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects; D019908:Proto-Oncogene Proteins c-raf; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D053630:Depsides
chemical_list: D001572:Benzofurans; D054377:Chemokine CXCL12; D051417:Focal Adhesion Kinase 1; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D019908:Proto-Oncogene Proteins c-raf; D019718:Receptors, CXCR4; C076944:salvianolic acid B; D053630:Depsides; C496052:Ptk2 protein, rat; C546782:Raf1 protein, rat