title: Endothelial RIG-I activation impairs endothelial function.
abstract: 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.
  
  
  RESULTS
  Wild type mice were injected intravenously with 32.5 μg 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Asdonk
authors.forename: Inga
authors.initials: I
authors.lastname: Motz
authors.forename: Nikos
authors.initials: N
authors.lastname: Werner
authors.forename: Christoph
authors.initials: C
authors.lastname: Coch
authors.forename: Winfried
authors.initials: W
authors.lastname: Barchet
authors.forename: Gunther
authors.initials: G
authors.lastname: Hartmann
authors.forename: Georg
authors.initials: G
authors.lastname: Nickenig
authors.forename: Sebastian
authors.initials: S
authors.lastname: Zimmer
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000201:enzymology*; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000096:biosynthesis* / Q000235:genetics; D004730:Endothelium, Vascular / Q000201:enzymology*; D006801:Humans; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism; D011971:Receptors, Immunologic
chemical_list: D017382:Reactive Oxygen Species; D011971:Receptors, Immunologic; C452820:RIGI protein, human; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases