Activated toll-like receptor 4 in monocytes is associated with heart failure after acute myocardial infarction

Abstract

Peripheral monocytosis may affect the development of heart failure (HF) after acute myocardial infarction (AMI). Activated toll-like receptor (TLR) 4 in monocytes plays an important role in the synthesis of proinflammatory cytokines. We examined TLR4 expression in monocytes, which may be a possible source of proinflammatory cytokines in AMI. Sixty-five patients with AMI and 20 healthy subjects (HS) were studied. Monocytes were isolated from peripheral blood on days 1 and 14 after the onset of AMI. TLR4 levels in monocytes were measured using real-time RT-PCR and flow cytometry. Generation capacity was evaluated by TLR4 levels and cytokine concentrations in the culture medium with lipopolysaccharide (LPS) stimulation. On day 1 after onset, baseline levels of TLR4 and plasma proinflammatory cytokines, notably IL-6 and TNF-α, were higher in AMI patients than in HS. These levels remained elevated in AMI patients 14 days after onset. Generation capacities of TLR4 and proinflammatory cytokines (IL-2, IL-6, IL-8, IL-10, GM-CSF and TNF-α) were increased in AMI patients compared to HS. LPS-stimulated TLR4 levels were positively correlated with IL-6 and TNF-α levels in AMI patients. Baseline TLR4 levels and plasma proinflammatory cytokine (IL-6, GM-CSF and TNF-α) levels were higher in AMI patients with HF ( n = 22) than in those without HF. Generation capacities of TLR4 and proinflammatory cytokines (IL-6, GM-CSF and TNF-α) were greater in AMI patients with HF than in those without HF. Activation of TLR4 through a myocytic inflammatory reaction is associated with HF after AMI. These observations suggest that TLR4 signaling in monocytes may play a role in the development of HF after AMI.