Tanshinone IIA inhibits smooth muscle proliferation and intimal hyperplasia in the rat carotid balloon-injured model through inhibition of MAPK signaling pathway

Aim of the study: To investigate the effect of tashinone IIA (TA) on intimal hyperplasia in a rat model of carotid artery balloon injury and on the proliferation of cultured vascular smooth muscle cells (VSMCs) induced by fetal bovine serum (FBS) and its underlying mechanisms. Materials and methods: Carotid artery injury was induced in rats by balloon dilatation and they were treated with TA or vehicle for 2 weeks until killed for assessment of neointimal formation and lumen area. VSMC was cultured in vitro and proliferation was assessed by determining cell number, bromodeoxyuridine (BrdU) incorporation and cell cycle analysis. The extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and c-fos expression were assessed by Western blot and reverse transcription-polymerase chain reaction (RT-PCR) respectively. Results: TA could significantly decrease intimal thickening, suppress cell proliferation and BrdU incorporation into DNA, block cell cycle in G(0)/G(1), phase, inhibit ERK1/2 phosphorylation and c-fos expression. Conclusions: TA abolishes VSMC proliferation and reduces intimal hyperplasia through inhibition of mitogen-activated protein kinase (MAPK) signaling pathway and down-regulation of c-fos expression. (C) 2010 Elsevier Ireland Ltd. All rights reserved.