Abstract
The mechanisms underlying the deterioration of patients with heart failure necessitating Left Ventricular Assist Device (LVAD) support remain poorly understood. Cytokines and effector molecules of the innate immune system have been implicated in the pathogenesis of heart failure. Toll Like Receptor 4 (TLR4) is thought to play a central role in the innate immune system. We have investigated TLR4 expression in the myocardium of a total of 39 patients and compared TLR4 expression in deteriorating patients requiring LVAD support (n = 11) to expression in patients with stable advanced heart failure undergoing heart transplantation (HF, n = 18). Quantitative Real Time PCR was used to measure TLR4 mRNA expression in left ventricular cores samples from LVAD candidates and left ventricular samples from patients undergoing heart transplantation. TLR4 expression was compared with TNF-α, IL1-β and IL6 expression in the same samples. TLR4 expression was 1.7-fold higher in the deteriorating LVAD candidates compared to the HF patients, p<0.05. IL1-β expression was 9.78-fold higher in the LVAD compared to HF patients, p<0.0001 and TLR4 expression correlated strongly with IL1-β expression (r = 0.7, p < 0.0001). TNF-α expression was also 1.8-fold higher (p<0.05) and IL6 expression was 2.2-fold higher (p<0.05) in LVAD compared to HF patients but the correlation between TLR4 and TNF-α and IL6 was poor in individual patients. It is concluded that TLR4 is increased in patients that require LVAD support. The exact mechanisms responsible, the pathways involved and their role in acute deterioration requires further investigation.
Published Version
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