| First Author | Papageorgiou AP | Year | 2015 |
| Journal | Cardiovasc Res | Volume | 107 |
| Issue | 1 | Pages | 78-88 |
| PubMed ID | 25998987 | Mgi Jnum | J:255732 |
| Mgi Id | MGI:6106190 | Doi | 10.1093/cvr/cvv157 |
| Citation | Papageorgiou AP, et al. (2015) Liver X receptor activation enhances CVB3 viral replication during myocarditis by stimulating lipogenesis. Cardiovasc Res 107(1):78-88 |
| abstractText | AIMS: 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. METHODS AND 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. CONCLUSION: LXR agonism does not modulate cardiac inflammation, but exacerbates virus-mediated myocardial damage during VM by stimulating lipid biosynthesis and enhancing CVB3 replication. |
