Emerging importance of chemokine receptor CXCR3 and its ligands in cardiovascular diseases

Raffaele Altara*, Marco Manca, Rita D. Brandao, Asad Zeidan, George W. Booz, Fouad A. Zouein

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    46 Citations (Web of Science)

    Abstract

    stract
    The CXC chemokines, CXCL4, -9, -10, -11, CXCL4L1, and the CC chemokine CCL21, activate CXC chemokine receptor 3 (CXCR3), a cell-surface G protein-coupled receptor expressed mainly by Th1 cells, cytotoxic T (Tc) cells and NK cells that have a key role in immunity and inflammation. However, CXCR3 is also expressed by vascular smooth muscle and endothelial cells, and appears to be important in controlling physiological vascular function. In the last decade, evidence from pre-clinical and clinical studies has revealed the participation of CXCR3 and its ligands in multiple cardiovascular diseases (CVDs) of different aetiologies including atherosclerosis, hypertension, cardiac hypertrophy and heart failure, as well as in heart transplant rejection and transplant coronary artery disease (CAD). CXCR3 ligands have also proven to be valid biomarkers for the development of heart failure and left ventricular dysfunction, suggesting an underlining pathophysiological relation between levels of these chemokines and the development of adverse cardiac remodelling. The observation that several of the above-mentioned chemokines exert biological actions independent of CXCR3 provides both opportunities and challenges for developing effective drug strategies. In this review, we provide evidence to support our contention that CXCR3 and its ligands actively participate in the development and progression of CVDs, and may additionally have utility as diagnostic and prognostic biomarkers.
    Original languageEnglish
    Pages (from-to)463-478
    Number of pages16
    JournalClinical Science
    Volume130
    Issue number7
    DOIs
    Publication statusPublished - 1 Apr 2016

    Keywords

    • atherosclerosis
    • cardiac hypertrophy
    • CXCL chemokines
    • heart failure
    • myocardial infarction
    • myocarditis
    • transplant coronary artery disease

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