title: The role of ERK1/2 signaling pathway in coronary microembolization-induced rat myocardial inflammation and injury.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Guangxi Medical University, Nanning, China. drlilang@163.com
authors.forename: Lang
authors.initials: L
authors.lastname: Li
authors.forename: Dong-Hua
authors.initials: DH
authors.lastname: Li
authors.forename: Nan
authors.initials: N
authors.lastname: Qu
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Wen
authors.forename: Wie-Qiang
authors.initials: WQ
authors.lastname: Huang
mesh_terms: D000818:Animals; D026481:Blotting, Far-Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000494:pharmacology; D054059:Coronary Occlusion / Q000150:complications* / Q000503:physiopathology*; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism / Q000502:physiology*; D009206:Myocardium / Q000473:pathology*; D010766:Phosphorylation; D058226:Plaque, Atherosclerotic / Q000150:complications; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D005419:Flavonoids; D014409:Tumor Necrosis Factor-alpha; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one