Increased toll-like receptor 4 in the myocardium of patients requiring left ventricular assist devices.

Abstract

BACKGROUND:

Cytokine activation in the myocardium of deteriorating patients with heart failure who undergo left ventricular assist-device (LVAD) implantation has been documented, but the underlying mechanisms remain poorly understood. We hypothesized the innate immune system is activated with expression of Toll-like receptor 4 (TLR4), leading to cytokine activation in these patients.

METHODS:

We used quantitative real-time reverse-transcriptase polymerase chain reaction to measure TLR4, interleukin-1 (IL-1) receptor, IL-1 beta, IL-6, and tumor necrosis factor alpha (TNF-alpha) mRNA expression in myocardial samples from 36 patients. We compared 18 patients who underwent LVAD implantation with 18 patients with less severe heart failure who underwent elective heart transplantation.

RESULTS:

Toll-like receptor 4 expression was 1.69-fold greater (p < 0.05) and IL-1 receptor expression was 3.64-fold greater (p < 0.0001) in the deteriorating patients who required LVADs. Myocardial TNF-alpha (1.71-fold, p < 0.05), IL-6 (2.57-fold, p < 0.005), and IL-1 beta (9.78-fold, p < 0.001) also were increased in the LVAD candidates. Toll-like receptor 4 expression correlated strongly with IL-1 receptor expression (r= 0.75, p < 0.0001) and with IL-1 beta expression in individual patients (r = 0.7, p < 0.0001). Interleukin-1 receptor expression also correlated with IL-1 beta expression (r = 0.78, p < 0.0001) within patients. We found no correlation between TLR4 and either TNF-alpha or IL-6 expression.

CONCLUSIONS:

Patients who required LVAD support showed evidence of innate immune system activation, indicated by an increase in the key effector molecule TLR4 associated with a specific pattern of cytokine expression in the myocardium.

• Authors: Emma J Birks, Leanne E Felkin, Nicholas R Banner, Asghar Khaghani, Paul J R Barton, Magdi H Yacoub
• Journal: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation (J Heart Lung Transplant) Vol. 23 Issue 2 Pg. 228-35 (Feb 2004) ISSN: 1053-2498 [Print] United States
• PMID: 14761771 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Interleukin-1
• Interleukin-6
• Membrane Glycoproteins
• RNA, Messenger
• Receptors, Cell Surface
• Receptors, Interleukin-1
• TLR4 protein, human
• Toll-Like Receptor 4
• Toll-Like Receptors
• Tumor Necrosis Factor-alpha

Topics

• Adult
• Cytokines (metabolism)
• Female
• Heart Failure (immunology, therapy)
• Heart-Assist Devices
• Humans
• Interleukin-1 (immunology)
• Interleukin-6 (immunology)
• Male
• Membrane Glycoproteins (immunology)
• Myocardium (immunology)
• RNA, Messenger (genetics)
• Receptors, Cell Surface (immunology)
• Receptors, Interleukin-1 (immunology)
• Reverse Transcriptase Polymerase Chain Reaction
• Toll-Like Receptor 4
• Toll-Like Receptors
• Tumor Necrosis Factor-alpha (immunology)