Organ Failure Key Laboratory of Ministry of Education, Department of Cardiology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, China.
Cardiovasc Res. 2011 Dec 1;92(3):385-93. doi: 10.1093/cvr/cvr221. Epub 2011 Aug 12.
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.
趋化因子（FKN）是一种新发现的膜结合趋化因子；其在心肌缺血和心力衰竭中的作用尚不清楚。我们试图研究 FKN 在心肌缺血以及缺血或压力超负荷诱导的心室重构和心力衰竭中的作用。
在培养的大鼠心肌细胞中检查了 FKN 诱导的与心力衰竭相关的基因变化，以及 FKN 在缺氧/复氧（A/R）期间对培养的心肌细胞损伤的影响。还研究了 FKN 中和对心力衰竭的直接影响及其潜在机制。在心力衰竭的小鼠中，心肌 FKN 表达与肺重/体重比、左心室缩短分数和脑钠肽表达相关。在培养的大鼠细胞中，FKN 暴露增加了心肌细胞中利钠肽 A 的表达、成纤维细胞中基质金属蛋白酶-9 的表达和微血管内皮细胞中细胞间黏附分子-1 的表达。FKN 还促进了 A/R 期间的心肌细胞损伤，中和 FKN 抗体治疗改善了心肌梗死或压力超负荷引起的心力衰竭。中和 FKN 或其受体抑制了低氧心肌细胞或缺血心肌中丝裂原激活蛋白激酶（MAPKs）的激活。
FKN 促进心肌损伤并加速心力衰竭的进展，这与 MAPKs 的激活有关。
