Increased expression of LIGHT/TNFSF14 and its receptors in experimental and clinical heart failure.
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.
Dahl
Christen Peder
CP
Research Institute for Internal Medicine, Rikshospitalet-Radiumhospitalet Medical Centre, University of Oslo, Norway. c.p.dahl@medisin.uio.no
Gullestad
Lars
L
Fevang
Børre
B
Holm
Are M
AM
Landrø
Linn
L
Vinge
Leif Erik
LE
Fiane
Arnt E
AE
Sandberg
Wiggo J
WJ
Otterdal
Kari
K
Frøland
Stig S
SS
Damås
Jan Kristian
JK
Halvorsen
Bente
B
Aukrust
Pål
P
Øie
Erik
E
Yndestad
Arne
A
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
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