Aims: 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.
Methods and results: 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.
Conclusion: FKN promotes myocardial injury and accelerates the progress of heart failure, which is associated with the activation of MAPKs.