The Role of ERK1/2 Signaling Pathway in Coronary Microembolization-Induced Rat Myocardial Inflammation and Injury


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Abstract

Aim:Inflammation plays an important role in coronary microembolization (CME)-induced myocardial injury. The present study was designed to investigate the role of extracellular signal-regulated kinases 1/2 (ERK1/2) signaling pathway in regulating myocardial inflammation and cardiac function in a rat model of CME.Methods:Sprague-Dawley rats were randomly divided into three groups: sham-operated group (sham group), CME group and PD98059 group (15 animals per group). CME was produced by injection of 42-μm microspheres into the left ventricle with occlusion of the ascending aorta. Rats in the PD98059 group were injected with PD98059, a specific ERK1/2 inhibitor, 30 min before the CME operation. Western blotting and immunohistochemistry analysis were used to determine the activation of ERK1/2. Echocardiography was employed to evaluate cardiac function. Hematoxylin-eosin staining was performed to assay myocardial inflammation. Expression of TNF-α mRNA was determined by RT-PCR analysis, and activity of NF-κB was assessed by electrophoretic mobility shift assay.Results:CME dramatically induced cardiac dysfunction (left ventricular ejection fraction, LVEF, was 72.97 ± 3.20% in the CME vs. 82.69 ± 3.50% in the sham group, p < 0.05) and local myocardial inflammatory response, both of which were ameliorated significantly by PD98059 (LVEF was 76.46 ± 4.46 and p < 0.05 vs. CME group). When compared to the CME group, PD98059 markedly attenuated the increased phosphorylation of ERK1/2 (0.48 ± 0.11 vs. 0.92 ± 0.10, p < 0.05), expression of TNF-α mRNA (0.42 ± 0.06 vs. 0.94 ± 0.04, p < 0.05) and activity of NF-κB (104.83 ± 13.65 vs. 540.79 ± 24.95, p < 0.05) in CME rat myocardium. Conclusions: The present study demonstrates a novel role of the ERK1/2 signaling pathway in promoting myocardium inflammation and dysfunction in CME, and suggests that ERK1/2 is a novel potential therapeutic target for CME.Copyright © 2010 S. Karger AG, Basel

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