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首页> 外文期刊>Journal of vascular research >Glucagon-Like Peptide-1 Receptor Activation Does Not Affect Re-Endothelialization but Reduces Intimal Hyperplasia via Direct Effects on Smooth Muscle Cells in a Nondiabetic Model of Arterial Injury
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Glucagon-Like Peptide-1 Receptor Activation Does Not Affect Re-Endothelialization but Reduces Intimal Hyperplasia via Direct Effects on Smooth Muscle Cells in a Nondiabetic Model of Arterial Injury

机译：胰高血糖素样肽1受体激活不影响内皮重塑，但通过在非糖尿病性动脉损伤模型中对平滑肌细胞的直接作用减少内膜增生。

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Diabetic patients have an increased risk of restenosis and late stent thrombosis after angioplasty, i.e. complications that are related to a defective re-endothelialization. Exendin-4, a stable glucagon-like peptide (GLP)-1 receptor agonist, has been suggested to influence the formation of intimal hyperplasia and to increase endothelial cell proliferation in vitro. Thus, the aim of this study was to investigate the mechanisms by which treatment with exendin-4 could influence re-endothelialization and intimal hyperplasia after vascular injury. Methods: Sprague-Dawley rats were subjected to balloon injury of the left common carotid artery and treated for 4 weeks with exendin-4 or vehicle. Intimal hyperplasia and vessel wall elasticity were monitored noninvasively by high-frequency ultrasound, and re-endothelialization was evaluated upon sacrifice using Evans blue dye. Results and Conclusion: Exendin-4 selectively reduced the proliferation of smooth muscle cells (SMCs) and intimal hyperplasia in vivo without affecting the re-endothelialization process, but treatment with exendin-4 improved arterial wall elasticity. Our data also show that exendin-4 significantly decreased the proliferation and increased the apoptosis of SMCs in vitro, effects that appear to be mediated through cAMP signaling and endothelial nitric oxide synthase following GLP-1 receptor activation. Together, these effects of exendin-4 are highly desirable and may lead to an improved outcome for patients undergoing vascular interventions. (C) 2015 S. Karger AG, Basel
机译：糖尿病患者在血管成形术后发生再狭窄和晚期支架血栓形成的风险增加，即与不良的再内皮化有关的并发症。已提出Exendin-4是一种稳定的胰高血糖素样肽（GLP）-1受体激动剂，可影响内膜增生的形成并在体外增加内皮细胞的增殖。因此，本研究的目的是研究用exendin-4进行治疗可影响血管损伤后再内皮化和内膜增生的机制。方法：对Sprague-Dawley大鼠进行左颈总动脉球囊损伤，并用exendin-4或媒介物治疗4周。通过高频超声无创地监测内膜增生和血管壁弹性，并使用伊文思蓝染料在处死后评估内皮重塑化。结果与结论：Exendin-4选择性地减少了体内平滑肌细胞（SMCs）的增殖和内膜增生，而没有影响内皮再形成过程，但是exendin-4的治疗改善了动脉壁的弹性。我们的数据还显示，exendin-4在体外显着降低SMC的增殖并增加其凋亡，这种作用似乎是通过cAMP信号传导和GLP-1受体激活后的内皮一氧化氮合酶介导的。总之，exendin-4的这些作用是非常令人希望的，并且可能会导致接受血管介入治疗的患者的预后得到改善。 （C）2015 S.Karger AG，巴塞尔

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