Therapeutic effect of magnesium lithospermate B on neointimal formation after balloon-induced vascular injury

被引：36

作者：

Hur, Kyu Yeon ^{[2
,3
]}

Seo, Hye Jun ^{[2
]}

Kang, Eun Seok ^{[1
,2
,3
]}

Kim, Soo Hyun ^{[3
]}

Song, Seungjeong ^{[4
]}

Kim, Eun Hee ^{[2
]}

Lim, Soyeon ^{[2
,5
]}

Choi, Chulhee ^{[4
]}

Heo, Ji Hoe ^{[2
,7
]}

Hwang, Ki Chul ^{[5
]}

Ahn, Chul Woo ^{[1
,2
,3
]}

Cha, Bong Soo ^{[1
,2
,3
]}

Jung, Mankil ^{[6
]}

Lee, Hyun Chul ^{[1
,2
,3
]}

机构：

[1] Yonsei Univ, Coll Med, Dept Internal Med, Seoul 120752, South Korea

[2] Yonsei Univ, Brain Korea Project Med Sci 21, Seoul 120752, South Korea

[3] Yonsei Univ, Coll Med, Inst Endocrine Res, Seoul 120752, South Korea

[4] Korea Adv Inst Sci & Technol, Dept Bio & Brain Engn, Taejon 305701, South Korea

[5] Yonsei Univ, Coll Med, Cardiovasc Res Inst, Div Cardiol, Seoul 120752, South Korea

[6] Yonsei Univ, Dept Chem, Seoul 120752, South Korea

[7] Yonsei Univ, Coll Med, Dept Neurol, Seoul 120752, South Korea

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2008年 / 586卷 / 1-3期

关键词：

magnesium lithospermate B; vascular smooth muscle cell; platelet-derived growth factor; reactive oxygen species; neointimal formation;

D O I：

10.1016/j.ejphar.2008.02.072

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Vascular smooth muscle cell (VSMC) proliferation and migration in response to platelet-derived growth factor (PDGF) play an important role in the development of atherosclerosis and restenosis. Recent evidence indicates that PDGF increases intracellular levels of reactive oxygen species in VSMCs and that both PDGF-induced VSMC proliferation and migration are reactive oxygen species-dependent. Danshen is a representative oriental medicine used for the treatment of vascular disease. Previously, we reported that magnesium lithospermate B, an active component of Danshen, is a potent antioxidant. Thus we investigated the therapeutic potential of magnesium lithospermate B in neointimal formation after carotid artery injury in rats along with its effects on the PDGF signaling pathway for stimulating VSMC proliferation and migration in vitro. PDGF is dimeric glycoprotein composed of two A or two B chains. In this study, we used PDGF-BB, which is one of the isoforms of PDGF (i.e., PDGF-AA, PDGF-BB, and PDGF-AB). Our results demonstrated that magnesium lithospermate B directly scavenged reactive oxygen species in a xanthine/xanthine oxidase system and reduced PDGF-BB-induced intracellular reactive oxygen species generation in VSMCs. In a rat carotid artery balloon injury model, magnesium lithospermate B treatment (10 mg/kg/day, i.p) showed a significant effect on the prevention of neointimal formation compared with vehicle treatment. In cultured VSMCs, magnesium lithospermate B significantly attenuated PDGF-BB-induced cell proliferation and migration as measured by 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2-tetrazolium bromide (MTT) assay and transwell migration assays, respectively. Further, magnesium lithospermate B inhibited PDGF-BB-induced phosphorylation of phospatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathways by scavenging reactive oxygen species. Together, these data indicated that magnesium lithospermate 13, a potent reactive oxygen species scavenger, prevented both injury-induced neointimal formation in vivo and PDGF-BB-induced VSMC proliferation and migration in vitro, suggesting that magnesium lithospermate B may be a promising agent to prevent atherosclerosis and restenosis following angioplasty. (c) 2008 Elsevier B.V. All rights reserved.

引用

页码：226 / 233

页数：8

共 37 条

[1] Platelet-derived growth factor-induced H2O2 production requires the activation of phosphatidylinositol 3-kinase [J].