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Cited by 150Atherosclerosis and Cardiovascular DiseasesChemokine receptors and signalingS100 Proteins and Annexins

The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.

Annexin A1 Counteracts Chemokine-Induced Arterial Myeloid Cell Recruitment

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Drechsler, Maik, de Jong, Renske, Rossaint, Jan, Viola, Joana R., Leoni, Giovanna, Wang, Ji Ming, Grommes, Jochen, Hinkel, Rabea, Kupatt, Christian, Weber, Christian, Döring, Yvonne, Zarbock, Alexander, Soehnlein, Oliver·2015·Circulation Research
DOI 10.1161/circresaha.116.305825PMC PMC7751381
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Abstract

Rationale: Chemokine-controlled arterial leukocyte recruitment is a crucial process in atherosclerosis. Formyl peptide receptor 2 (FPR2) is a chemoattractant receptor that recognizes proinflammatory and proresolving ligands. The contribution of FPR2 and its proresolving ligand annexin A1 to atherosclerotic lesion formation is largely undefined. Objective: Because of the ambivalence of FPR2 ligands, we here investigate the role of FPR2 and its resolving ligand annexin A1 in atherogenesis. Methods and Results: Deletion of FPR2 or its ligand annexin A1 enhances atherosclerotic lesion formation, arterial myeloid cell adhesion, and recruitment. Mechanistically, we identify annexin A1 as an endogenous inhibitor of integrin activation evoked by the chemokines CCL5, CCL2, and CXCL1. Specifically, the annexin A1 fragment Ac2-26 counteracts conformational activation and clustering of integrins on myeloid cells evoked by CCL5, CCL2, and CXCL1 through inhibiting activation of the small GTPase Rap1. In vivo administration of Ac2-26 largely diminishes arterial recruitment of myeloid cells in a FPR2-dependent fashion. This effect is also observed in the presence of selective antagonists to CCR5, CCR2, or CXCR2, whereas Ac2-26 was without effect when all 3 chemokine receptors were antagonized simultaneously. Finally, repeated treatment with Ac2-26 reduces atherosclerotic lesion sizes and lesional macrophage accumulation. Conclusions: Instructing the annexin A1-FPR2 axis harbors a novel approach to target arterial leukocyte recruitment. With the ability of Ac2-26 to counteract integrin activation exerted by various chemokines, delivery of Ac2-26 may be superior in inhibition of arterial leukocyte recruitment when compared with blocking individual chemokine receptors.

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Metadata

Authors
Drechsler, M., de Jong, R., Rossaint, J., Viola, J. R., Leoni, G., Wang, J. M., Grommes, J., Hinkel, R., Kupatt, C., Weber, C., Döring, Y., Zarbock, A., & Soehnlein, O.
Affiliations
  • National Institutes of Health (US)
  • From the Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich, Germany (M.D., R.d.J., J.R.V., G.L., J.G., C.W., Y.D., O.S.); Department of Pathology, Academic Medical Center (AMC), Amsterdam University, Amsterdam, The Netherlands (M.D., O.S.); Department of Anaesthesiology, University Münster, Münster, Germany (J.R., A.Z.); Max Planck Institute, Münster, Germany (J.R., A.Z.); Laboratory of Molecular Immunoregulation, NCI, Frederick, MD (J.M.W.); European Vascular Center Aachen...
ORCID
Venue
Circulation Research
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2015-02-27
Volume
116
Issue
5
Pages
827-835
ISSN
  • 0009-7330 (ISSN-L)
  • 1524-4571
DOI
10.1161/circresaha.116.305825
PMC
PMC7751381
OpenAlex
W2100320418
Cited by
150
References
44
Citations by year
2026: 3 · 2025: 16 · 2024: 8 · 2023: 8 · 2022: 22 · 2021: 14 · 2020: 9 · 2019: 15 · 2018: 17 · 2017: 9 · 2016: 17 · 2015: 12
FWCI
5.79
Type
journal article
Language
en
Open access
Locations
  • Circulation Research (publishedVersion)
  • Research Publications (Maastricht University) (publishedVersion, other-oa)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • mediaTUM (Technical University of Munich) (submittedVersion)
  • RWTH Publications (RWTH Aachen) (submittedVersion)
  • Research Publications (Maastricht University) (submittedVersion, other-oa)
Funders
  • National Institutes of Health
  • National Cancer Institute (Z01BC010015)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › S100 Proteins and Annexins
Keywords
annexin A1, formyl peptide receptor 2, atherosclerosis, integrin activation, Rap1, chemokines, RANTES, MCP-1, CXCL1, Ac2-26, macrophage accumulation, chemokine receptor antagonists
MeSH terms
Animals, Aortic Diseases, Apolipoproteins E, Chemotaxis, Dietary Fats, Mice, Inbred C57BL, Peptides, Annexin A1, Mice, Knockout, Chemokine CCL2, Chemokine CCL5, Receptors, CCR5, rap1 GTP-Binding Proteins, Myeloid Cells, Receptors, Interleukin-8B, Receptors, Formyl Peptide, Atherosclerosis, Mice, Chemokine CXCL1, Receptors, CCR2

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