Detrimental effect of fractalkine on myocardial ischaemia and heart failure

Wanling Xuan, Yulin Liao, Baihe Chen, Qiaobing Huang, Dingli Xu, Yili Liu, Jianping Bin, Masafumi Kitakaze

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

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 resultsFKN-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.ConclusionFKN promotes myocardial injury and accelerates the progress of heart failure, which is associated with the activation of MAPKs.

Original languageEnglish (US)
Pages (from-to)385-393
Number of pages9
JournalCardiovascular Research
Volume92
Issue number3
DOIs
StatePublished - Dec 1 2011
Externally publishedYes

Keywords

  • Fractalkine
  • Heart failure
  • Mitogen-activated protein kinases
  • Myocardial ischaemia

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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  • Cite this

    Xuan, W., Liao, Y., Chen, B., Huang, Q., Xu, D., Liu, Y., Bin, J., & Kitakaze, M. (2011). Detrimental effect of fractalkine on myocardial ischaemia and heart failure. Cardiovascular Research, 92(3), 385-393. https://doi.org/10.1093/cvr/cvr221