Endothelial RIG-I activation impairs endothelial function
Endothelial RIG-I activation impairs endothelial function
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DOI：
10.1016/j.bbrc.2012.02.116
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发表时间：
2012-03-30
影响因子：
3.1
通讯作者：
Zimmer, Sebastian
中科院分区：
文献类型：
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作者：
Asdonk, Tobias;Motz, Inga;Zimmer, Sebastian
背景资料：内皮功能障碍是慢性炎症性动脉粥样硬化过程的重要组成部分，并由先天性和获得性免疫机制介导。最近的研究表明，模式识别受体（PRR）专门识别的核酸可能在内皮生物学中发挥重要作用，在致动脉粥样硬化的方式。在这里，我们分析了内皮视黄酸诱导基因I（RIG-I）激活血管内皮biology.Methods和结果的影响：野生型小鼠静脉注射32.5微克的RIG配体3 pRNA（RNA与三磷酸在5 '端）或polyA控制每隔一天7天。在3 pRNA处理的小鼠中，与对照组相比，内皮依赖性血管舒张显著受损，血管氧化应激显著增加，循环内皮微粒（EMP）数量显著升高。为了进一步了解RIG-I依赖性内皮生物学，用3 pRNA体外刺激培养的人冠状动脉内皮细胞（HCAEC）和内皮祖细胞（EPC）。两种细胞类型都表达RIG-I，并在刺激时与受体上调反应。活性氧（ROS）的形成在这两种细胞类型中增强，而细胞凋亡和增殖在HCAEC中没有显着影响。重要的是，HCAEC释放显着量的促炎细胞因子响应RIG-I stimulation.Conclusion：这项研究表明，激活的细胞质核酸受体RIG-I导致内皮功能障碍。因此，RIG-I诱导的内皮损伤可能是动脉粥样硬化形成的重要途径。(C)2012 Elsevier Inc. All rights reserved.
Background: Endothelial dysfunction is a crucial part of the chronic inflammatory atherosclerotic process and is mediated by innate and acquired immune mechanisms. Recent studies suggest that pattern recognition receptors (PRR) specialized in immunorecognition of nucleic acids may play an important role in endothelial biology in a proatherogenic manner. Here, we analyzed the impact of endothelial retinoic acid inducible gene I (RIG-I) activation upon vascular endothelial biology.Methods and results: Wild type mice were injected intravenously with 32.5 mu g of the RIG-ligand 3pRNA (RNA with triphosphate at the 5'end) or polyA control every other day for 7 days. In 3pRNA-treated mice, endothelium-depended vasodilation was significantly impaired, vascular oxidative stress significantly increased and circulating endothelial microparticle (EMP) numbers significantly elevated compared to controls. To gain further insight in RIG-I dependent endothelial biology, cultured human coronary endothelial cells (HCAEC) and endothelial progenitor cells (EPC) were stimulated in vitro with 3pRNA. Both cells types express RIG-I and react with receptor upregulation upon stimulation. Reactive oxygen species (ROS) formation is enhanced in both cell types, whereas apoptosis and proliferation is not significantly affected in HCAEC. Importantly, HCAEC release significant amounts of proinflammatory cytokines in response to RIG-I stimulation.Conclusion: This study shows that activation of the cytoplasmatic nucleic acid receptor RIG-I leads to endothelial dysfunction. RIG-I induced endothelial damage could therefore be an important pathway in atherogenesis. (C) 2012 Elsevier Inc. All rights reserved.