Mechanisms of ERK1/2 signaling pathway participate in inflammatory reaction caused by coronary heart disease / 天津医药

ABSTRACT

Objective To investigate the effects of ERK1/2 signaling pathway on coronary atherosclerosis-associated inflammatory reaction in autopsy cases. Methods Forty-five autopsy cases were divided into three groupscoronary arterydisease (CHD)-associated death group, CHD group and control group (n=15 for each group). The inflammatory cell infiltration in myocardial tissues was observed through staining leucocyte common antigen (CD45) by HE and immunohistochemistry method. The protein expression level and distribution in extracellular signal-regulated kinase 1/2 (t-ERK1/2) and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) of myocardial tissues were detected by immunohistochemistry and Western-blot assay. The expression level of tumor necrosis factor α (TNF-α) was determined using semiquantitative RT-PCR analysis. The activity of nuclear factor (NF)-κB was assessed using electrophoretic mobility shift assay (EMSA). Results Compared with CHD and control groups, myocardial inflammatory cell counts, phosphorylation of ERK1/2, TNF-α mRNA expression and NF-κB activation were significantly increased in CHD-associated death group (P < 0.05). Western blot analysis showed that the phosphorylation of ERK1/2 was positively correlated with expression of TNF-αmRNA and the number of inflammatory cells in CHD-associated death group (r=0.675, P<0.01;r=0.893, P<0.01). Conclusion Results reveal that the activation of ERK1/2 signaling pathway is considered as an important mechanism for coronary atherosclerosis caused myocardial inflammatory reaction, which indicates that the inhibition of ERK1/2 signal transduction pathway may become a potential new target for prevention and treatment of atherosclerotic coronary infarction.