Role of inflammatory chemokines in hypertension

Mikolajczyk, T. P., Szczepaniak, P., Vidler, F., Maffia, P. , Graham, G. J. and Guzik, T. J. (2021) Role of inflammatory chemokines in hypertension. Pharmacology and Therapeutics, 223, 107799. (doi: 10.1016/j.pharmthera.2020.107799) (PMID:33359600)

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Hypertension is associated with immune cells activation and their migration into the kidney, vasculature, heart and brain. These inflammatory mechanisms are critical for blood pressure regulation and mediate target organ damage, creating unique novel targets for pharmacological modulation. In response to angiotensin II and other pro-hypertensive stimuli, the expression of several inflammatory chemokines and their receptors is increased in the target organs, mediating homing of immune cells. In this review, we summarize the contribution of key inflammatory chemokines and their receptors to increased accumulation of immune cells in target organs and effects on vascular dysfunction, remodeling, oxidative stress and fibrosis, all of which contribute to blood pressure elevation. In particular, the role of CCL2, CCL5, CXCL8, CXCL9, CXCL10, CXCL11, CXCL16, CXCL1, CX3CL1, XCL1 and their receptors in the context of hypertension is discussed. Recent studies have tested the efficacy of pharmacological or genetic targeting of chemokines and their receptors on the development of hypertension. Promising results indicate that some of these pathways may serve as future therapeutic targets to improve blood pressure control and prevent target organ consequences including kidney failure, heart failure, atherosclerosis or cognitive impairment.

Item Type:Articles
Additional Information:Funding sources: Our lab is supported by the Polish National Centre for Research and Development (ERA-CVD/NEMO/7/2019 - TPM and ERA-CVD/PLAQUEFIGHT/5/2018 - TJG); the Mobility Plus Program of Polish Ministry of Science and Higher Education (1280/MOB/IV/2015/0 -TPM); the European Research Council (Project Identifier: 726318 - TJG); the British Heart Foundation grants (PG/19/84/34771 - PM and RE/13/5/30177); the Wellcome Trust grant (204820/Z/16/Z - PM and TJG); and the University of Glasgow Scottish Funding Council and the Global Challenges Research Fund - PM and TJG. Work in GJG's lab is supported by the a Wellcome Investigator Award (217093/Z/19/Z) and an MRC Programme Grant (MR/M019764/1).
Glasgow Author(s) Enlighten ID:Maffia, Professor Pasquale and Szczepaniak, Mr Piotr and Mikolajczyk, Dr Tomasz and Guzik, Professor Tomasz and Vidler, Ms Francesca and Graham, Professor Gerard
Authors: Mikolajczyk, T. P., Szczepaniak, P., Vidler, F., Maffia, P., Graham, G. J., and Guzik, T. J.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Research Centre:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
Journal Name:Pharmacology and Therapeutics
ISSN (Online):1879-016X
Published Online:24 December 2020

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
308639Defining the individual and integrated roles of inflammatory chemokine receptors (iCCRs) in atherosclerosisPasquale MaffiaBritish Heart Foundation (BHF)PG/19/84/34771CAMS - Cardiovascular Science
190814BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177Institute of Cardiovascular & Medical Sciences
173707Institutional Strategic Support Fund (2016)Anna DominiczakWellcome Trust (WELLCOTR)204820/Z/16/ZInstitute of Cardiovascular & Medical Sciences
306649Defining chemokine receptor involvement in the myelomonocytic inflammatory responseGerard GrahamWellcome Trust (WELLCOTR)217093/Z/19/ZIII - Immunology
171627The ACKR2-CCR2 axis in development and diseaseGerard GrahamMedical Research Council (MRC)MR/M019764/1III - Immunology