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Fractalkine Signalling (CX₃CL1/CX₃CR1 Axis) as an Emerging Target in Coronary Artery Disease.

Lookup NU author(s): Shu Xian Loh, Yasemin Ekinci, Dr Luke Spray, Dr Visvesh Jeyalan, Professor Gavin RichardsonORCiD, Dr David Austin, Dr Mohammad Alkhalil, Professor Ioakim SpyridopoulosORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

Acute myocardial infarction (MI) is the most common and dramatic complication of atherosclerosis, which, despite successful reperfusion therapy, can lead to incident heart failure (HF). HF occurs when the healing process is impaired due to adverse left ventricular remodelling, and can be the result of so-called ischaemia/reperfusion injury (IRI), visualised by the development of intramyocardial haemorrhage (IMH) or microvascular obstruction (MVO) in cardiac MRI. Thus far, translation of novel pharmacological strategies from preclinical studies to target either IRI or HF post MI have been largely unsuccessful. Anti-inflammatory therapies also carry the risk of affecting the immune system. Fractalkine (FKN, CX₃CL1) is a unique chemokine, present as a transmembrane protein on the endothelium, or following cleavage as a soluble ligand, attracting leukocyte subsets expressing the corresponding receptor CX₃CR1. We have shown previously that the fractalkine receptor CX₃CR1 is associated with MVO in patients undergoing primary PCI. Moreover, inhibition of CX₃CR1 with an allosteric small molecule antagonist (KAND567) in the rat MI model reduces acute infarct size, inflammation, and IMH. Here we review the cellular biology of fractalkine and its receptor, along with ongoing studies that introduce CX₃CR1 as a future target in coronary artery disease, specifically in patients with myocardial infarction.

Publication metadata

Author(s): Loh SX, Ekinci Y, Spray L, Jeyalan V, Olin T, Richardson G, Austin D, Alkhalil M, Spyridopoulos I

Publication type: Article

Publication status: Published

Journal: J. Clin. Med.

Year: 2023

Volume: 12

Issue: 14

Online publication date: 21/07/2023

Acceptance date: 19/07/2023

Date deposited: 21/07/2023

ISSN (electronic): 2077-0383

Publisher: MDPI AG

URL: https://doi.org/10.3390/jcm12144821

DOI: 10.3390/jcm12144821

PubMed id: 21045240

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