Expression of Toll-like Receptor 4 on Peripheral Blood Mononuclear Cells and Its Effects on Patients with Acute Myocardial Infarction Treated with Thrombolysis

Background and Aims. TLR4 has been shown to mediate inflammation in animal models of myocardial ischemia/reperfusion injury (MI/RI). Here we hypothesized that TLR4 on peripheral blood mononuclear cells (PBMCs) may be involved in the inflammatory response in this type of clinical event. Methods. Seventy two patients with acute myocardial infarction (AMI) who underwent thrombolysis were assigned into reperfusion group (n = 43) and non-reperfusion group (n = 29) according to recanalization of infarct-related artery (IRA) and 40 healthy volunteers were enrolled in this experiment. Eight mL of venous blood was taken from all patients 0 h before and 2, 6, 12, and 24 h after thrombolysis. Flow cytometry (FCM) was used to detect TLR4 protein expression and real-time quantitative RT-PCR was performed to determine TLR4 mRNA and myeloid differentiation protein-88 (Myd88) mRNA expression. The concentration of tumor necrosis factor-alpha (TNF-alpha) in plasma was evaluated using enzyme-linked immunosorbent assay (ELISA). Results. Compared with controls, all detected indicators in AMI patients were upregulated before thrombolysis (p <0.01). After thrombolysis, they were further increased. In re:perfusion group, all attained their peaks in earlier hours and the peak values were lower compared with non-reperfusion group. In both cases, either reperfusion or non-perfusion., TLR4 mRNA expression was positively correlated with the levels of Myd88 mRNA (r = 0.886 and 0.694, p <0.01), respectively. Conclusions. TLR4 expression on PBMCs was markedly elevated in AMI patients either reperfused or non-reperfused. Inflammatory reaction by activated TLR4 in MI/RI in patients may be through TLR4-Myd88-dependent signal pathway. (C) 2010 IMSS. Published by Elsevier Inc.