title: Emerging importance of chemokine receptor CXCR3 and its ligands in cardiovascular diseases.
abstract: 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.
authors.affiliation: 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. raltara@umc.edu.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Altara
authors.affiliation: DG-DI, Medical Applications, CERN, 1211 Geneva 23, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Manca
authors.affiliation: Maastricht Science Programme, Maastricht University, 6200 MD Maastricht, The Netherlands.
authors.forename: Rita D
authors.initials: RD
authors.lastname: Brandão
authors.affiliation: Department of Anatomy, Cell Biology and Physiology, American University of Beirut Faculty of Medicine, Beirut 1107 2020, Lebanon.
authors.forename: Asad
authors.initials: A
authors.lastname: Zeidan
authors.affiliation: Department of Pharmacology and Toxicology, School of Medicine, University of Mississippi Medical Center, Jackson, MS 39216-4505, U.S.A.
authors.forename: George W
authors.initials: GW
authors.lastname: Booz
authors.affiliation: Department of Pharmacology and Toxicology, American University of Beirut Faculty of Medicine, Beirut 1107 2020, Lebanon.
authors.forename: Fouad A
authors.initials: FA
authors.lastname: Zouein
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D002317:Cardiovascular Agents / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D002319:Cardiovascular System / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D019743:Chemokines, CXC / Q000378:metabolism*; D015195:Drug Design; D006801:Humans; D008024:Ligands; D058990:Molecular Targeted Therapy; D011237:Predictive Value of Tests; D011379:Prognosis; D054367:Receptors, CXCR3 / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D015415:Biomarkers; C515187:CXCR3 protein, human; D002317:Cardiovascular Agents; D019743:Chemokines, CXC; D008024:Ligands; D054367:Receptors, CXCR3
keywords: CXCL chemokines; atherosclerosis; cardiac hypertrophy; heart failure; myocardial infarction; myocarditis; transplant coronary artery disease