Thromb Haemost 2019; 119(04): 534-541
DOI: 10.1055/s-0038-1676988
Theme Issue Article
Georg Thieme Verlag KG Stuttgart · New York

Atypical Chemokine Receptors in Cardiovascular Disease

Selin Gencer*
1  Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich, Germany
,
Emiel P. C. van der Vorst*
1  Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich, Germany
,
Maria Aslani
1  Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich, Germany
,
Christian Weber
1  Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich, Germany
2  German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
3  Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
,
Yvonne Döring*
1  Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich, Germany
2  German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
,
Johan Duchene*
1  Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich, Germany
› Author Affiliations
Funding The authors' research is supported by the DFG (SFB1123 TP A1) to Y.D. and C.W., by the DFG (SFB1123 TP A10) to J.D. and C.W. and by the Alexander von Humboldt Foundation to E.P.C.v.d.V.
Further Information

Publication History

17 October 2018

21 November 2018

Publication Date:
04 February 2019 (eFirst)

Abstract

Inflammation has been well recognized as one of the main drivers of atherosclerosis development and therefore cardiovascular diseases (CVDs). It has been shown that several chemokines, small 8 to 12 kDa cytokines with chemotactic properties, play a crucial role in the pathophysiology of atherosclerosis. Chemokines classically mediate their effects by binding to G-protein-coupled receptors called chemokine receptors. In addition, chemokines can also bind to atypical chemokine receptors (ACKRs). ACKRs fail to induce G-protein-dependent signalling pathways and thus subsequent cellular response, but instead are able to internalize, scavenge or transport chemokines. In this review, we will give an overview of the current knowledge about the involvement of ACKR1–4 in CVDs and especially in atherosclerosis development. In the recent years, several studies have highlighted the importance of ACKRs in CVDs, although there are still several controversies and unexplored aspects that have to be further elucidated. A better understanding of the precise role of these atypical receptors may pave the way towards novel and improved therapeutic strategies.

Note

After the acceptance of the current manuscript, a study by Girbl T et al demonstrating a new function for ACKR1 in leukocyte trafficking was published. This study showed that ACKR1, not only is involved in leukocyte adhesion11, but can also regulate leukocyte transendothelial migration. Indeed, CXCL2 produced by neutrophils is deposited on ACKR1 at endothelial junctions, and ACKR1-presented CXCL2 facilitates unidirectional luminal-to-abluminal migration of neutrophils.[95]


* These authors contributed equally to the manuscript and share first or last authorship.