Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Atypical Roles of the Chemokine Receptor ACKR3/CXCR7 in Platelet Pathophysiology

Version 1 : Received: 21 December 2021 / Approved: 22 December 2021 / Online: 22 December 2021 (12:27:01 CET)

A peer-reviewed article of this Preprint also exists.

Chatterjee, M. Atypical Roles of the Chemokine Receptor ACKR3/CXCR7 in Platelet Pathophysiology. Cells 2022, 11, 213. Chatterjee, M. Atypical Roles of the Chemokine Receptor ACKR3/CXCR7 in Platelet Pathophysiology. Cells 2022, 11, 213.

Journal reference: Cells 2022, 11, 213
DOI: 10.3390/cells11020213

Abstract

The manifold actions of the pro-inflammatory and regenerative chemokine CXCL12/SDF-1α are executed through the canonical GProteinCoupledReceptor CXCR4, and the non-canonical ACKR3/CXCR7. Platelets express CXCR4, ACKR3/CXCR7, and are a vital source of CXCL12/SDF-1α themselves. In recent years, a regulatory impact of the CXCL12-CXCR4-CXCR7 axis on platelet biogenesis i.e. megakaryopoiesis, thrombotic and thrombo-inflammatory ac-tions have been revealed through experimental and clinical studies. Platelet surface expression of ACKR3/CXCR7 is significantly enhanced following myocardial infarction (MI) in acute coro-nary syndrome (ACS) patients, also associated with improved functional recovery and progno-sis. The therapeutic implications of ACKR3/CXCR7 in myocardial regeneration and improved recovery following an ischemic episode, are well documented. Cardiomyocytes, cardi-ac-fibroblasts, endothelial lining of the blood vessels perfusing the heart, besides infiltrating platelets and monocytes, all express ACKR3/CXCR7. This review recapitulates ligand induced differential trafficking of platelet CXCR4-ACKR3/CXCR7 affecting their surface availability, and in regulating thrombo-inflammatory platelet functions and survival through CXCR4 or ACKR3/CXCR7. It emphasizes the pro-thrombotic influence of CXCL12/SDF-1α exerted through CXCR4, as opposed to the anti-thrombotic impact of ACKR3/CXCR7. Offering an innovative translational perspective, this review also discusses the advantages and challenges of utilizing ACKR3/CXCR7 as a potential anti-thrombotic strategy in platelet associated cardiovascular dis-orders, particularly in coronary artery disease (CAD) patients post-MI.

Keywords

Platelet; ACKR3/CXCR7; Thrombosis; Thrombo-inflammation; Anti-platelet therapy; Cardiovascular disease; Coronary artery disease

Subject

MEDICINE & PHARMACOLOGY, General Medical Research

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