Elevated circulating levels of heat shock protein 70 are related to systemic inflammatory reaction through monocyte Toll signal in patients with heart failure after acute myocardial infarction.
BACKGROUND
Recent studies have shown that heat shock protein (HSP) 70 may serve as a "damage signal" to the immune system and could be the endogenous ligand for Toll-like receptor (TLR) 4 mediating synthesis of inflammatory cytokines.


OBJECTIVE
To explore the relationship between circulating HSP70 levels and activation of monocyte TLR4 and myocardial damage after AMI.


RESULTS
This study examined circulating HSP70 and monocyte TLR4 levels in 52 patients with AMI and 20 controls, and analyzed ex vivo inflammatory cytokine productions using HSP70-stimulated monocytes. Circulating HSP70 levels were higher in AMI patients on day 1 after onset than in controls and remained elevated in AMI patients 14 days after onset. HSP70 levels were positively correlated with monocyte TLR4, plasma interleukin-6 and tumor necrosis factor-alpha levels in AMI patients. HSP70 levels 14 days after onset were higher in AMI patients with heart failure (n=15) than in those without heart failure. In our in vitro study, HSP70-stimulated monocytes resulted in dose-dependent TLR4 expression and release of inflammatory cytokines. TLR4 antibody inhibited inflammatory cytokines release.


CONCLUSIONS
Elevated circulating levels of HSP70 may be involved in TLR4 signal-mediated immune response and the progression of heart failure after AMI.
Satoh
Mamoru
M
Second Department of Internal Medicine, Iwate Medical University School of Medicine, Uchimaru 19-1, Morioka 020-8505, Iwate, Japan. m_satoh@imu.ncvc.go.jp
Shimoda
Yudai
Y
Akatsu
Tomonari
T
Ishikawa
Yuh
Y
Minami
Yoshitaka
Y
Nakamura
Motoyuki
M
D000208:Acute Disease; D002478:Cells, Cultured; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000097:blood*; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D009203:Myocardial Infarction / Q000150:complications / Q000378:metabolism*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D018840:HSP70 Heat-Shock Proteins; D015850:Interleukin-6; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha