Expression of Toll-like receptor 4 on peripheral blood mononuclear cells and its effects on patients with acute myocardial infarction treated with thrombolysis.
OBJECTIVE
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-α (TNF-α) 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 reperfusion 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.
Department of Cardiology, the First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei Province, China.
Jun
J
Yang
Lv-ying
LY
Jin
Jia-wang
JW
Ding
Yong-qin
YQ
Zhou
Jian
J
Yang
Rui-Yang
Li-li
D000328:Adult; D000368:Aged; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D009203:Myocardial Infarction / Q000097:blood* / Q000235:genetics* / Q000628:therapy; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000235:genetics; D011446:Prospective Studies; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D015398:Signal Transduction; D015912:Thrombolytic Therapy; D051197:Toll-Like Receptor 4 / Q000097:blood* / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015854:Up-Regulation
D017931:DNA Primers; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha