Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA.
J Surg Res. 2011 Nov;171(1):31-9. doi: 10.1016/j.jss.2011.03.018. Epub 2011 Apr 1.
Neointimal 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.
GA 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.
GA-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.
GA-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.
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）连接，以确定 GA 传递对新生内膜形成的影响。
GA 在 overnight incubation 中与 80nm GNP 连接。用不同剂量的 GA-GNP、GA 单独、GNP 单独和无处理对照处理小鼠 P53LMAC01 血管 SMC。分析细胞增殖和迁移，测定超氧阴离子水平和 ERK1/2 的磷酸化状态。小鼠进行颈总动脉结扎，局部给予 GNP（对照）或 GA-GNP 治疗。收获颈总动脉并进行免疫组织化学分析。
与单独用 GNP 处理相比，GA-GNP 处理显著抑制了 SMC 的体外增殖和迁移，并且这种作用在处理后持续长达 72 小时。GA-GNP 处理还降低了体外的超氧阴离子水平。PDGF-BB 可显著诱导 GNP 对照细胞中 ERK1/2 的磷酸化；与仅用 GNP 处理相比，GA-GNP 处理的细胞中这种 PDGF-BB 诱导的 ERK1/2 磷酸化明显受到抑制。GA-GNP 显著减少了小鼠损伤后的内膜增生，并且在接受 GA-GNP 治疗的小鼠的动脉中，增殖细胞核抗原（PCNA）染色明显减少。
GA-GNP 通过降低 ERK1/2 的激活，减少体外血管 SMC 的增殖和迁移。动脉损伤部位局部给予 GA-GNP 可减少新生内膜增生和随后的狭窄。
