title: Increased expression of LIGHT/TNFSF14 and its receptors in experimental and clinical heart failure.
abstract: BACKGROUND
  Clinical and experimental studies suggest a pathogenic role for inflammation in chronic heart failure (HF). LIGHT is a member of the tumour necrosis factor superfamily involved in innate and adaptive immune responses.
  
  
  OBJECTIVE
  We sought to investigate a potential pathogenic role of LIGHT in chronic HF.
  
  
  METHODS
  We used various clinical and experimental approaches including studies in post-infarction HF rats and in vitro studies of endothelial cells and peripheral blood mononuclear cells (PBMC).
  
  
  RESULTS
  Our main findings were: (i) LIGHT and its receptors (i.e., HVEM and lymphotoxin-beta receptor) were regulated during experimental HF, with strong expression in the infarcted area accompanied by up-regulation of HVEM in cardiomyocytes and endothelial cells also in the non-ischaemic part of the left ventricle. (ii) Patients with chronic HF had significantly increased expression of LIGHT on CD3(+) T-cells accompanied by increased expression of HVEM on monocytes and within the failing myocardium. (iii) LIGHT induced interleukin (IL)-6 expression in endothelial cells. In HF patients, but not in healthy controls, such an IL-6-inducing effect was also seen in LIGHT activated PBMC.
  
  
  CONCLUSIONS
  Our findings in both clinical and experimental HF may suggest a role for LIGHT signalling pathways in the progression of chronic HF involving IL-6-related mechanisms.
authors: Research Institute for Internal Medicine, Rikshospitalet-Radiumhospitalet Medical Centre, University of Oslo, Norway. c.p.dahl@medisin.uio.no
authors: Christen Peder
authors: CP
authors: Dahl
authors: Lars
authors: L
authors: Gullestad
authors: Børre
authors: B
authors: Fevang
authors: Are M
authors: AM
authors: Holm
authors: Linn
authors: L
authors: Landrø
authors: Leif Erik
authors: LE
authors: Vinge
authors: Arnt E
authors: AE
authors: Fiane
authors: Wiggo J
authors: WJ
authors: Sandberg
authors: Kari
authors: K
authors: Otterdal
authors: Stig S
authors: SS
authors: Frøland
authors: Jan Kristian
authors: JK
authors: Damås
authors: Bente
authors: B
authors: Halvorsen
authors: Pål
authors: P
authors: Aukrust
authors: Erik
authors: E
authors: Øie
authors: Arne
authors: A
authors: Yndestad
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D006333:Heart Failure / Q000473:pathology*; D006352:Heart Ventricles / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism; D053259:Lymphotoxin beta Receptor / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009203:Myocardial Infarction / Q000473:pathology; D032383:Myocytes, Cardiac / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000473:pathology; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D017252:CD3 Complex; D015850:Interleukin-6; D053259:Lymphotoxin beta Receptor; D053240:Receptors, Tumor Necrosis Factor, Member 14; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14