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

Abstract

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. Aims: To explore the relationship between circulating HSP70 levels and activation of monocyte TLR4 and myocardial damage after AMI. Methods and 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-α 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. © 2006 European Society of Cardiology.