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


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.
Li
Xin
X
State Key Laboratory of Biotherapy, West China Medical School, Sichuan University, Chengdu, China.
Du
Jun-Rong
JR
Yu
Yan
Y
Bai
Bo
B
Zheng
Xiao-Yuan
XY
D045784:Abietanes; D000800:Angioplasty, Balloon; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002339:Carotid Arteries / Q000473:pathology; D020212:Carotid Artery Injuries / Q000188:drug therapy / Q000473:pathology; D018929:Cell Culture Techniques; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006965:Hyperplasia; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology; D010616:Phenanthrenes / Q000494:pharmacology* / Q000627:therapeutic use; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology
D045784:Abietanes; D010616:Phenanthrenes; D010936:Plant Extracts; D016760:Proto-Oncogene Proteins c-fos; C021751:tanshinone; D004247:DNA; D048049:Extracellular Signal-Regulated MAP Kinases; D001973:Bromodeoxyuridine