Abstract 3603: Elevated Circulating Levels of Heat Shock Protein 70 Activate Monocyte Toll Signal in Patients with Heart Failure After Acute Myocardial Infarction
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. Monocyte-related inflammatory cytokines may contribute to the inflammatory and subsequent immune responses after acute myocardial infarction (AMI). However, the relationship between HSP70 and TLR4 signal in AMI patients has remained unknown. Our objective was to explore the relationship between circulating HSP70 levels and activation of monocyte TLR4 and myocardial damage after AMI. This study examined circulating HSP70 and monocyte TLR4 levels in 52 patients with AMI (mean age, 64.9 ±1.5; male / female, 37 / 15) and 20 healthy subjects (mean age, 63.7 ± 1.7; male / female, 14 / 6) as controls, and analyzed in vitro inflammatory cytokine productions using HSP70-stimulated monocytes. Circulating HSP70 levels were higher in AMI patients on day 1 after onset than in controls (1254.4 ± 102.3 pg / mL vs. 545.3 ± 11.5 pg / mL, P < 0.01), and remained elevated in AMI patients 14 days after onset (625.8 ± 15.3 pg / mL, P < 0.05). HSP70 levels were positively correlated with monocyte TLR4 (HSP70 vs. TLR4 protein, r = 0.65, P <0.01; HSP70 vs. TLR4 mRNA, r = 0.66, P < 0.01), plasma interleukin-6 (IL−6, r = 0.42, P < 0.01) and tumor necrosis factor−α levels (TNF−α, r = 0.37, P = 0.01) in AMI patients. Circulating HSP70 levels 14 days after onset were higher in AMI patients with heart failure (n = 15) than in those without heart failure (637.5 ± 40.2 pg / mL vs. 448.7 ± 32.4 pg / mL, P < 0.01). HSP70 levels 14 days after AMI were negatively correlated with left ventricular ejection fraction (r = −0.44, P = 0.01). In our in vitro study, recombinant human HSP70-stimulated monocytes resulted in dose-dependent TLR4 expression and release of IL−6 and TNF−α. TLR4 antibody inhibited IL−6 and TNF−α release. The present study has demonstrated a close link between circulating HSP70 and monocyte TLR4 signal in AMI patients. Increased HSP70 levels may be involved in TLR4-mediated immune response and the progression of heart failure after AMI.