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

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-mu m 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-alpha mRNA was determined by RT-PCR analysis, and activity of NF-kappa B 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-alpha mRNA (0.42 +/- 0.06 vs. 0.94 +/- 0.04, p < 0.05) and activity of NF-kappa B (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 (C) 2010 S. Karger AG, Basel