title: Liver X receptor activation enhances CVB3 viral replication during myocarditis by stimulating lipogenesis.
abstract: OBJECTIVE
  Viral myocarditis (VM) is severe cardiac inflammation that can result in sudden death or congestive heart failure in previously healthy adults, with no effective therapy. Liver X receptor (LXR) agonists have both anti-inflammatory and lipid-lowering properties. This study investigates whether LXR agonist T0901317 may modulate viral replication and cardiac inflammation during VM.
  
  
  RESULTS
  (i) Adult mice were administered T0901317 or vehicle with the onset of inflammation during CVB3 virus myocarditis or (ii) treated 2 days prior to CVB3 infection. Against what we expected, T0901317 treatment did not alter leucocyte infiltration after CVB3 infection; yet pre-administration with T0901317 resulted in increased mortality upon CVB3 infection, higher cardiac viral presence, and increased cardiomyocyte damage when compared with the vehicle. Furthermore, we show a correlation of fatty acid synthase (FAS) and sterol regulatory element-binding protein 1c (SREBP-1c) with CVB3 viral load in the heart and that T0901317 is able to enhance the cardiac expression of FAS and SREBP-1c. Finally, we show in vitro that T0901317 is able to exaggerate CVB3-mediated damage of Vero cells, whereas inhibitors of FAS and the SREBP-1c reduce the viral presence of CVB3 in neonatal cardiomyocytes.
  
  
  CONCLUSIONS
  LXR agonism does not modulate cardiac inflammation, but exacerbates virus-mediated myocardial damage during VM by stimulating lipid biosynthesis and enhancing CVB3 replication.
authors.affiliation: Centre for Molecular and Vascular Biology (CMVB), Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium CArdiovascular Research Institute Maastricht (CARIM), Universiteitssingel 50, 6229 ER Maastricht, The Netherlands anna.papageorgiou@maastrichtuniversity.nl.
authors.forename: Anna-Pia
authors.initials: AP
authors.lastname: Papageorgiou
authors.affiliation: Centre for Molecular and Vascular Biology (CMVB), Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium CArdiovascular Research Institute Maastricht (CARIM), Universiteitssingel 50, 6229 ER Maastricht, The Netherlands.
authors.forename: Ward
authors.initials: W
authors.lastname: Heggermont
authors.affiliation: CArdiovascular Research Institute Maastricht (CARIM), Universiteitssingel 50, 6229 ER Maastricht, The Netherlands.
authors.forename: Marieke
authors.initials: M
authors.lastname: Rienks
authors.affiliation: Centre for Molecular and Vascular Biology (CMVB), Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium CArdiovascular Research Institute Maastricht (CARIM), Universiteitssingel 50, 6229 ER Maastricht, The Netherlands.
authors.forename: Paolo
authors.initials: P
authors.lastname: Carai
authors.affiliation: Laboratory of Intensive Care Medicine, KU Leuven, Leuven, Belgium.
authors.forename: Lies
authors.initials: L
authors.lastname: Langouche
authors.affiliation: CArdiovascular Research Institute Maastricht (CARIM), Universiteitssingel 50, 6229 ER Maastricht, The Netherlands.
authors.forename: Wouter
authors.initials: W
authors.lastname: Verhesen
authors.affiliation: University Medical Center, Groningen University, Groningen, The Netherlands.
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: De Boer
authors.affiliation: Centre for Molecular and Vascular Biology (CMVB), Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium CArdiovascular Research Institute Maastricht (CARIM), Universiteitssingel 50, 6229 ER Maastricht, The Netherlands ICIN - Netherlands Heart Institute, Utrecht, The Netherlands.
authors.forename: Stephane
authors.initials: S
authors.lastname: Heymans
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003384:Coxsackievirus Infections / Q000150:complications / Q000401:mortality; D050171:Dyslipidemias / Q000209:etiology; D029822:Enterovirus B, Human / Q000502:physiology*; D050155:Lipogenesis; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009205:Myocarditis / Q000821:virology*; D057093:Orphan Nuclear Receptors / Q000502:physiology*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000037:antagonists & inhibitors / Q000502:physiology; D014779:Virus Replication
chemical_list: D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D051780:Sterol Regulatory Element Binding Protein 1
keywords: Inflammation; Lipids; Liver X receptors; Myocarditis; Viral replication