Ginkgolide A-gold nanoparticles inhibit vascular smooth muscle proliferation and migration in vitro and reduce neointimal hyperplasia in a mouse model.
Ginkgolide A-gold nanoparticles inhibit vascular smooth muscle proliferation and migration in vitro and reduce neointimal hyperplasia in a mouse model.
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银杏内酯 A-金纳米粒子在体外抑制血管平滑肌增殖和迁移，并减少小鼠模型中的新生内膜增生。
DOI：
10.1016/j.jss.2011.03.018
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Chen,Changyi
中科院分区：
文献类型：
--
作者：
Weakley,SarahM;Wang,Xinwen;Mu,Hong;Lü,Jianming;Lin,PeterH;Yao,Qizhi;Chen,Changyi
新生内膜的形成是由血管平滑肌细胞（SMC）的表型变化介导的，是动脉重建后再狭窄的重要介质。我们将抗氧化剂银杏内酯A（GA）与金纳米颗粒（GNP）结合，以确定GA递送对新生内膜形成的影响。用各种剂量的GA-GNP、单独的GA、单独的GNP和无处理对照处理小鼠P53LMAC01血管SMC。分析细胞增殖和迁移，并测定超氧阴离子水平和ERK 1/2磷酸化状态。对小鼠进行颈总动脉沿着结扎，并用GNP（对照）或GA-GNP局部处理。取颈动脉行免疫组化分析，与GNP单独处理相比，TSGA-GNP处理显著抑制SMC的增殖和迁移，并且这种作用持续至处理后72 h。用GA-GNP处理还降低了体外超氧阴离子水平。PDGF-BB在GNP对照细胞中显著诱导ERK 1/2磷酸化;与仅GNP相比，GA-GNP处理的细胞中PDGE-BB诱导的ERK 1/2磷酸化被显著抑制。GA-GNP显着减少小鼠损伤后的新生内膜增生，增殖细胞核抗原（PCNA）染色显着减少与GA-GNP治疗的小鼠动脉中。结论SGA-GNP通过减少ERK 1/2的激活，减少血管平滑肌细胞增殖和迁移。在动脉损伤区域用GA-GNP局部治疗减少了新生内膜增生和随后的狭窄。
BACKGROUNDNeointimal formation is mediated by phenotypic changes in vascular smooth muscle cells (SMC) and is an important mediator of restenosis following arterial reconstruction. We conjugated antioxidant ginkgolide A (GA) to gold nanoparticles (GNP) to determine the effect of GA delivery on neointimal formation.MATERIALS AND METHODSGA was conjugated to 80 nm GNP in an overnight incubation. Mouse P53LMAC01 vascular SMC were treated with various doses of GA-GNP, GA alone, GNP alone, and no treatment control. Cell proliferation and migration were analyzed, and superoxide anion levels and the phosphorylation status of ERK1/2 were determined. Mice underwent ligation of the common carotid artery along with local treatment with GNP (control) or GA-GNP. The carotid artery was harvested and subjected to immunohistochemical analysis.RESULTSGA-GNP treatment significantly inhibited SMC proliferation and migration in vitro in comparison to GNP treatment alone, and the effect persisted for up to 72 h after treatment. Treatment with GA-GNP also reduced superoxide anion levels in vitro. PDGF-BB substantially induced ERK1/2 phosphorylation in GNP control cells; this PDGE-BB induced ERK1/2 phosphorylation was significantly inhibited in GA-GNP-treated cells compared with GNP only. GA-GNP significantly reduced neointimal hyperplasia after injury in mice, and proliferating cell nuclear antigen (PCNA) staining was reduced substantially in the arteries of mice treated with GA-GNP.CONCLUSIONSGA-GNP reduce vascular SMC proliferation and migration in vitro through reduced activation of ERK1/2. Local treatment with GA-GNP in areas of arterial injury reduced neointimal hyperplasia and subsequent stenosis.