title: Detrimental effect of fractalkine on myocardial ischaemia and heart failure.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  FKN promotes myocardial injury and accelerates the progress of heart failure, which is associated with the activation of MAPKs.
authors.affiliation: Organ Failure Key Laboratory of Ministry of Education, Department of Cardiology,  Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515,  China.
authors.forename: Wanling
authors.initials: W
authors.lastname: Xuan
authors.forename: Yulin
authors.initials: Y
authors.lastname: Liao
authors.forename: Baihe
authors.initials: B
authors.lastname: Chen
authors.forename: Qiaobing
authors.initials: Q
authors.lastname: Huang
authors.forename: Dingli
authors.initials: D
authors.lastname: Xu
authors.forename: Yili
authors.initials: Y
authors.lastname: Liu
authors.forename: Jianping
authors.initials: J
authors.lastname: Bin
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D002478:Cells, Cultured; D054428:Chemokine CX3CL1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D004789:Enzyme Activation; D005347:Fibroblasts / Q000378:metabolism; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D012720:Severity of Illness Index; D013997:Time Factors; D020257:Ventricular Remodeling
chemical_list: D057134:Antibodies, Neutralizing; D054428:Chemokine CX3CL1; C515539:Cx3cl1 protein, mouse; C515540:Cx3cl1 protein, rat; D011994:Recombinant Proteins; D020097:Natriuretic Peptide, Brain; D018799:Intercellular Adhesion Molecule-1; D009320:Atrial Natriuretic Factor; D020928:Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9