Cardiovasc Res 2011 Dec;92 (3): 385-93. [IF:6.051]
Detrimental effect of fractalkine on myocardial ischaemia and heart failure.
Xuan W , Liao Y , Chen B , Huang Q , Xu D , Liu Y , Bin J , Kitakaze M .
Organ Failure Key Laboratory of Ministry of Education, Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, China.
广州南方医科大学南方医院心内科，教育部器官功能衰竭防治省部共建重点实验室
Abstract
Fractalkine (FKN) is a newly identified membrane-bound chemokine; its role in myocardial ischaemia and heart failure is largely unknown. We attempted to investigate the role of FKN in myocardial ischaemia and ischaemia or pressure overload-induced ventricular remodelling and heart failure. FKN-induced changes of heart failure-related genes in cultured rat cardiac cells and the effect of FKN on cultured cardiomyocyte injury during anoxia/reoxygenation (A/R) were examined. The direct influence of FKN neutralization on heart failure and the potential mechanism was also investigated. In mice with failing hearts, myocardial FKN expression was correlated with the lung weight/body weight ratio, left ventricular fractional shortening, and brain natriuretic peptide expression. In cultured rat cells, exposure to FKN increased natriuretic peptide A expression in cardiomyocytes, matrix metalloproteinase-9 expression in fibroblasts, and intercellular adhesion molecule-1 expression in microvascular endothelial cells. FKN also promoted cardiomyocyte damage during A/R and neutralizing FKN antibody treatment improved heart failure induced by myocardial infarction or pressure overload. Neutralizing FKN or its receptor inhibited the activation of mitogen-activated protein kinases (MAPKs) in hypoxic cardiomyocytes or ischaemic myocardium. FKN promotes myocardial injury and accelerates the progress of heart failure, which is associated with the activation of MAPKs.
摘要：
Fractalkine(FKN)是一种新发现的膜结合趋化因子,它在心肌缺血和心力衰竭方面的作用大部分还不明确。我们试图探讨FKN在心肌缺血和缺血或压力负荷过大而引起的心室重塑和心力衰竭中的作用。实验项目包括FKN诱导的大鼠心脏细胞心力衰竭相关基因的改变和FKN在缺氧/ 复氧(A / R)过程中培养的心肌细胞损伤的影响。 FKN中立作用直接影响心力衰竭和潜在机制也在研究中。小鼠衰竭心脏模型中,心肌FKN表达与肺重/体重比、左心室缩短分数和脑利钠肽的表达相关。在培养的大鼠细胞模型中，FKN作用后心肌细胞利钠肽A表达增加、成纤维细胞基质金属蛋白酶-9表达增加，微血管内皮细胞细胞间粘附分子-1的表达增加。FKN也促进了A / R过程中心肌细胞损伤，同时中和FKN抗体疗法促进心肌梗死或压力过高引起的心力衰竭。在低氧心肌细胞或缺血细胞中中和FKN或其受体抑制活化蛋白激酶(MAPKs)的活性。FKN促进心肌损伤，加速心力衰竭,与MAPKs的激活相关。
