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Activated toll-like receptor 4 in monocytes is associated with heart failure after acute myocardial infarction
Mamoru Satoh1, Yudai Shimoda, Chihaya Maesawa
1Second Department of Internal Medicine, Iwate Medical University School of Medicine Uchimaru 19-1, Morioka, Iwate, Japan. m_satoh@imu.ncvc.go.jp
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-alpha, 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-alpha) were increased in AMI patients compared to HS. LPS-stimulated TLR4 levels were positively correlated with IL-6 and TNF-alpha levels in AMI patients. Baseline TLR4 levels and plasma proinflammatory cytokine (IL-6, GM-CSF and TNF-alpha) 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-alpha) 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.
Insights
Peripheral monocytosis and elevated toll-like receptor 4 (TLR4) in monocytes are linked to heart failure (HF) development after acute myocardial infarction (AMI). Increased TLR4 activation and cytokine production in AMI patients, especially those with HF, suggest a key role in disease progression.
Area of Science:
- Immunology
- Cardiology
- Molecular Biology
Background:
- Peripheral monocytosis may influence heart failure (HF) development post-acute myocardial infarction (AMI).
- Activated toll-like receptor 4 (TLR4) on monocytes is implicated in proinflammatory cytokine synthesis.
Purpose of the Study:
- To investigate TLR4 expression in monocytes as a potential source of proinflammatory cytokines in AMI.
- To assess the association between TLR4 activation, cytokine production, and HF development after AMI.
Main Methods:
- Monocytes were isolated from 65 AMI patients and 20 healthy subjects (HS) on days 1 and 14 post-AMI.
- TLR4 levels were quantified using real-time RT-PCR and flow cytometry.
- Monocyte generation capacity was evaluated via TLR4 levels and cytokine concentrations post-lipopolysaccharide (LPS) stimulation.
Main Results:
- AMI patients exhibited higher baseline TLR4 and plasma proinflammatory cytokine (IL-6, TNF-alpha) levels compared to HS, persisting at day 14.
- Increased generation capacity for TLR4 and multiple cytokines (IL-2, IL-6, IL-8, IL-10, GM-CSF, TNF-alpha) was observed in AMI patients.
- Elevated baseline and stimulated TLR4 levels, along with specific cytokines (IL-6, GM-CSF, TNF-alpha), were significantly higher in AMI patients who developed HF.
Conclusions:
- Activation of TLR4 signaling in monocytes is associated with HF development following AMI.
- These findings suggest that TLR4-mediated monocyte activation plays a crucial role in the pathogenesis of HF post-AMI.
