TY - JOUR
T1 - G-Protein Coupled Receptor Targeting on Myeloid Cells in Atherosclerosis
AU - van der Vorst, Emiel P. C.
AU - Peters, Linsey J. F.
AU - Mueller, Madeleine
AU - Gencer, Selin
AU - Yan, Yi
AU - Weber, Christian
AU - Döring , Yvonne
N1 - Funding Information:
This research was supported by the DFG (SFB1123 TP A1) to YD and CW, by the European Research Council (AdG◦692511) to CW, and by the Alexander von Humboldt Foundation, a grant from the Interdisciplinary Center for Clinical Research within the Faculty of Medicine at the RWTH Aachen University, the DZHK (German Centre for Cardiovascular Research), and the BMBF (German Ministry of Education and Research to EvdV.
Publisher Copyright:
Copyright © 2019 van der Vorst, Peters, Müller, Gencer, Yan, Weber and Döring. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
PY - 2019/5/22
Y1 - 2019/5/22
N2 - Atherosclerosis, the underlying cause of the majority of cardiovascular diseases (CVDs), is a lipid-driven, inflammatory disease of the large arteries. Gold standard therapy with statins and the more recently developed proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have improved health conditions among CVD patients by lowering low density lipoprotein (LDL) cholesterol. Nevertheless, a substantial part of these patients is still suffering and it seems that 'just' lipid lowering is insufficient. The results of the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) have now proven that inflammation is a key driver of atherosclerosis and that targeting inflammation improves CVD outcomes. Therefore, the identification of novel drug targets and development of novel therapeutics that block atherosclerosis-specific inflammatory pathways have to be promoted. The inflammatory processes in atherosclerosis are facilitated by a network of immune cells and their subsequent responses. Cell networking is orchestrated by various (inflammatory) mediators which interact, bind and induce signaling. Over the last years, G-protein coupled receptors (GPCRs) emerged as important players in recognizing these mediators, because of their diverse functions in steady state but also and specifically during chronic inflammatory processes - such as atherosclerosis. In this review, we will therefore highlight a selection of these receptors or receptor sub-families mainly expressed on myeloid cells and their role in atherosclerosis. More specifically, we will focus on chemokine receptors, both classical and atypical, formyl-peptide receptors, the chemerin receptor 23 and the calcium-sensing receptor. When information is available, we will also describe the consequences of their targeting which may hold promising options for future treatment of CVD.
AB - Atherosclerosis, the underlying cause of the majority of cardiovascular diseases (CVDs), is a lipid-driven, inflammatory disease of the large arteries. Gold standard therapy with statins and the more recently developed proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have improved health conditions among CVD patients by lowering low density lipoprotein (LDL) cholesterol. Nevertheless, a substantial part of these patients is still suffering and it seems that 'just' lipid lowering is insufficient. The results of the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) have now proven that inflammation is a key driver of atherosclerosis and that targeting inflammation improves CVD outcomes. Therefore, the identification of novel drug targets and development of novel therapeutics that block atherosclerosis-specific inflammatory pathways have to be promoted. The inflammatory processes in atherosclerosis are facilitated by a network of immune cells and their subsequent responses. Cell networking is orchestrated by various (inflammatory) mediators which interact, bind and induce signaling. Over the last years, G-protein coupled receptors (GPCRs) emerged as important players in recognizing these mediators, because of their diverse functions in steady state but also and specifically during chronic inflammatory processes - such as atherosclerosis. In this review, we will therefore highlight a selection of these receptors or receptor sub-families mainly expressed on myeloid cells and their role in atherosclerosis. More specifically, we will focus on chemokine receptors, both classical and atypical, formyl-peptide receptors, the chemerin receptor 23 and the calcium-sensing receptor. When information is available, we will also describe the consequences of their targeting which may hold promising options for future treatment of CVD.
KW - G-protein coupled receptors
KW - myeloid cells
KW - cardiovascular disease
KW - atherosclerosis
KW - therapy
KW - CALCIUM-SENSING-RECEPTOR
KW - ATYPICAL CHEMOKINE RECEPTORS
KW - FORMYL-PEPTIDE RECEPTOR
KW - EPICARDIAL ADIPOSE-TISSUE
KW - TYPE-2 DIABETES-MELLITUS
KW - DUFFY ANTIGEN RECEPTOR
KW - BETA-GAMMA-SUBUNITS
KW - RESOLVIN E1
KW - CA2+-SENSING RECEPTOR
KW - INTERNATIONAL UNION
U2 - 10.3389/fphar.2019.00531
DO - 10.3389/fphar.2019.00531
M3 - (Systematic) Review article
C2 - 31191301
SN - 1663-9812
VL - 10
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
M1 - 531
ER -