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Activation of epidermal growth factor receptor mediates myocardial ischemia/reperfusion arrhythmias in anaesthetized rats
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作者 MEI Feng~2,JI Zhou-xiang~1,QIN Fu~1,LEI Yang~1,HUI Liu~1 (1.Department of Pharmacology,Tongji Medical College, Huazhong University of Science and Technology,Wuhan 4300074 2.Department of Anesthesiology,Union Hospital, Tongji Medical College,Huazhong University of Science and Technology,Wuhan 4300074) 《岭南心血管病杂志》 2011年第S1期222-222,共1页
Objectives Epidermal growth factor receptor (EGFR)is a receptor protein tyrosine kinase and plays a critical role in the development and function of the heart.Previous studies have demonstrated that EGFR is involved... Objectives Epidermal growth factor receptor (EGFR)is a receptor protein tyrosine kinase and plays a critical role in the development and function of the heart.Previous studies have demonstrated that EGFR is involved in regulating electrical excitability of the heart.The present study was designed to investigate whether EGFR activation would mediate myocardial arrhythmias induced by ischemia/reperfu- sion in anaesthetized rats.Methods and results Myocardial ischemia/reperfusion arrhythmias were induced by 10 min ligation of the left anterior descending coronary artery,followed by a 30 min reperfusion in anaesthetized rats.Incidence and severity of cardiac arrhythmias were significantly reduced by pretreatment with the EGFR kinase inhibitor AG556.Phosphorylation level of myocardial EGFR was increased during ischemia and at early reperfusion.Intramyocardial transfection of EGFR siRNA reduced EGFR mRNA and protein,and decreased the incidence of ventricular fibrillation induced by reperfusion.Interestingly,tyrosine phosphorylation levels of cardiac Na<sup>+</sup> channel(I<sub>Na</sub>) and L-type Ca<sup>2+</sup> channel(I<sub>Ca.l</sub>) were significantly increased at corresponding time points to the alteration of phosphorylated EGFR level during reperfusion.AG556 pretreatment countered the increased tyrosine phosphorylation level of Na<sup>+</sup> and L-type Ca<sup>2+</sup> channels induced by reperfusion.No significant alteration was observed in tyrosine phosphorylation levels of cardiac Kv4.2 and Kir2.1 channels during the cardiac ischemia/reperfusion. Conclusions These results demonstrate for the first time that EGFR plays an important role in the genesis of myocardial ischemia/reperfusion arrhythmias,which is likely mediated at least in part by enhancing tyrosine phosphorylation of cardiac Na<sup>+</sup> and L-type Ca<sup>2+</sup> channels. 展开更多
关键词 EGFR Activation of epidermal growth factor receptor mediates myocardial ischemia/reperfusion arrhythmias in anaesthetized rats
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