Activated toll-like receptor 4 in monocytes is associated with heart failure after acute myocardial infarction.
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.
Satoh
Mamoru
M
Second Department of Internal Medicine, Iwate Medical University School of Medicine Uchimaru 19-1, Morioka, Iwate, Japan. m_satoh@imu.ncvc.go.jp
Shimoda
Yudai
Y
Maesawa
Chihaya
C
Akatsu
Tomonari
T
Ishikawa
Yuh
Y
Minami
Yoshitaka
Y
Hiramori
Katsuhiko
K
Nakamura
Motoyuki
M
D000368:Aged; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D009203:Myocardial Infarction / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013318:Stroke Volume; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
D016207:Cytokines; D018836:Inflammation Mediators; D051197:Toll-Like Receptor 4