Endothelial RIG-I activation impairs endothelial function

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• 作者：Tobias Asdonk^a ; ^{tobias.asdonk@ukb.uni-bonn.de} ; Inga Motz^a ; Nikos Werner^a ; Christoph Coch^b ; Winfried Barchet^b ; Gunther Hartmann^b ; Georg Nickenig^a ; Sebastian Zimmer^a
• 关键词：Endothelial biology ; RIG-I ; Atherosclerosis ; Inflammation ; Innate immune system
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：30 March, 2012
• 卷：420
• 期：1
• 页码：66-71
• 文件大小：304 K

摘要

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 渭g of the RIG-ligand 3pRNA (RNA with triphosphate at the 5鈥瞖nd) 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.