Soluble CD40 ligand in acute and chronic heart failure.
OBJECTIVE
Inflammatory cytokines may play a pathogenic role in heart failure (HF). CD40-CD40 ligand (CD40L) interactions are important in atherogenesis and based on its role in inflammation we sought to evaluate the role of CD40L in human HF.


RESULTS
Serum levels of soluble (s) CD40L were measured in 236 patients with acute HF following myocardial infarction, treated with either angiotensin-converting enzyme (ACE)-inhibition or angiotensin II blockade and followed for 2 years, and in 116 patients with chronic HF. Our main findings were: (i) patients with acute HF had increased sCD40L levels, particularly those with severe HF, diabetes, or hypertension; (ii) when these patients were followed longitudinally, persistently raised sCD40L levels were found throughout the observation period with no effect of captopril or losartan; (iii) the increase in sCD40L during follow-up was not seen in patients receiving warfarin therapy; (iv) patients with chronic HF also had raised sCD40L, significantly correlated with clinical severity, neurohormonal dysregulation, and left ventricular dysfunction; (v) studies from different blood compartments suggest that the vasculature of lower extremities and the failing myocardium itself may produce and secrete sCD40L in chronic HF.


CONCLUSIONS
Our findings may suggest a pathogenic role for enhanced CD40-CD40L interactions in human HF.
Ueland
Thor
T
Research Institute for Internal Medicine, Rikshospitalet University Hospital, N-0027 Oslo, Norway. thor.ueland@klinmed.uio.no
Aukrust
Pål
P
Yndestad
Arne
A
Otterdal
Kari
K
Frøland
Stig S
SS
Dickstein
Kenneth
K
Kjekshus
John
J
Gullestad
Lars
L
Damås
Jan K
JK
D000208:Acute Disease; D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D023201:CD40 Ligand / Q000378:metabolism*; D002216:Captopril / Q000627:therapeutic use; D002908:Chronic Disease; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood*; D016896:Treatment Outcome
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D023201:CD40 Ligand; D002216:Captopril; D019808:Losartan