Soluble CD40 ligand in acute and chronic heart failure.

Abstract

AIMS:

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.

METHODS AND 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.

CONCLUSION:

Our findings may suggest a pathogenic role for enhanced CD40-CD40L interactions in human HF.

• Authors: Thor Ueland, Pål Aukrust, Arne Yndestad, Kari Otterdal, Stig S Frøland, Kenneth Dickstein, John Kjekshus, Lars Gullestad, Jan K Damås
• Journal: European heart journal (Eur Heart J) Vol. 26 Issue 11 Pg. 1101-7 (Jun 2005) ISSN: 0195-668X [Print] England
• PMID: 15716285 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Angiotensin-Converting Enzyme Inhibitors
• CD40 Ligand
• Captopril
• Losartan

Topics

• Acute Disease
• Adult
• Aged
• Angiotensin II Type 1 Receptor Blockers (therapeutic use)
• Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
• CD40 Ligand (metabolism)
• Captopril (therapeutic use)
• Chronic Disease
• Female
• Heart Failure (blood, drug therapy)
• Humans
• Losartan (therapeutic use)
• Male
• Middle Aged
• Myocardial Infarction (blood)
• Treatment Outcome