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.
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April 2016
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Radiation nephropathy is mitigated by EET-A and also by captopril. The severe histological injury of radiation nephropathy includes cast formation and mesangiolysis. Both are significantly attenuated by EET-A or captopril. PAS stained kidney, 200x magnification. For further details see pp. 587–599. Image kindly provided by Dr. Md Abdul Hye Khan.
Review Article|
February 17 2016
Emerging importance of chemokine receptor CXCR3 and its ligands in cardiovascular diseases
Raffaele Altara;
*Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216–4505, U.S.A.
†Department of Pharmacology and Toxicology, School of Medicine, University of Mississippi Medical Center, Jackson, MS 39216–4505, U.S.A.
Correspondence: Raffaele Altara (email [email protected]).
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Marco Manca;
Marco Manca
‡DG-DI, Medical Applications, CERN, 1211 Geneva 23, Switzerland
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Rita D. Brandão;
Rita D. Brandão
§Maastricht Science Programme, Maastricht University, 6200 MD Maastricht, The Netherlands
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Asad Zeidan;
Asad Zeidan
║Department of Anatomy, Cell Biology and Physiology, American University of Beirut Faculty of Medicine, Beirut 1107 2020, Lebanon
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George W. Booz;
George W. Booz
†Department of Pharmacology and Toxicology, School of Medicine, University of Mississippi Medical Center, Jackson, MS 39216–4505, U.S.A.
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Fouad A. Zouein
Fouad A. Zouein
¶Department of Pharmacology and Toxicology, American University of Beirut Faculty of Medicine, Beirut 1107 2020, Lebanon
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Publisher: Portland Press Ltd
Received:
September 21 2015
Revision Received:
December 01 2015
Accepted:
December 03 2015
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 Authors; published by Portland Press Limited
2016
Clin Sci (Lond) (2016) 130 (7): 463–478.
Article history
Received:
September 21 2015
Revision Received:
December 01 2015
Accepted:
December 03 2015
Citation
Raffaele Altara, Marco Manca, Rita D. Brandão, Asad Zeidan, George W. Booz, Fouad A. Zouein; Emerging importance of chemokine receptor CXCR3 and its ligands in cardiovascular diseases. Clin Sci (Lond) 1 April 2016; 130 (7): 463–478. doi: https://doi.org/10.1042/CS20150666
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