ArticleCirculation research2015
Annexin A1 counteracts chemokine-induced arterial myeloid cell recruitment.
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Article in Circulation research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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87 citing papers in PubMed, 153 citations in OpenAlex.
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- Biomechanical signaling of cytoskeleton and membrane reorganization in tumor immune chemotactic migration.Theranostics · 2026Review
- Inflammation-resolution signalling in cardiac repair, remodelling, and heart failure.European heart journal open · 2025Review
- Formyl peptide receptor 1 and its antagonist T0080 in atherosclerosis.Cell death and differentiation · 2025Article
- Inflammation resolution-based treatment of atherosclerosis using biomimetic nanocarriers loaded with specialized pro-resolving lipid mediators.Materials today. Bio · 2025Article
- Cardiomyocyte proliferation: Advances and insights in macrophage-targeted therapy for myocardial injury.Genes & diseases · 2025Review
- Anti-Inflammatory Lipid Mediators from Polyunsaturated Fatty Acids: Insights into their Role in Atherosclerosis Microenvironments.Current atherosclerosis reports · 2025Review
- Article
- Annexin A: Cell Death, Inflammation, and Translational Medicine.Journal of inflammation research · 2025Review
- Annexin A8 deficiency delays atherosclerosis progression.Clinical and translational medicine · 2025Article
- Specialized pro-resolving mediators in vascular inflammation and atherosclerotic cardiovascular disease.Nature reviews. Cardiology · 2024Review
- Development of an Inflamed High Throughput Stem-cell-based Gut Epithelium Model to Assess the Impact of Annexin A1.Stem cell reviews and reports · 2024Article
- Neutrophil migration participates in the side effect of recombinant human tissue plasminogen activator.CNS neuroscience & therapeutics · 2024Article
- Beyond host defense and tissue injury: the emerging role of neutrophils in tissue repair.American journal of physiology. Cell physiology · 2024Review
- Review
- Stimulation of the Pro-Resolving Receptor Fpr2 Reverses Inflammatory Microglial Activity by Suppressing NFκB Activity.International journal of molecular sciences · 2023Article
- Molecular characterization and functional implications on mouse peripheral blood mononuclear cells of annexin proteins from Echinococcus granulosus sensu lato.Parasites & vectors · 2023Article
- Neutrophils in the periodontium: Interactions with pathogens and roles in tissue homeostasis and inflammation.Immunological reviews · 2023Review
27 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 1 institution in 2 countries.
Maik DrechslerFrom 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-Maastricht, University Hospital RWTH Aachen, Aachen, Germany (J.G.); Medizinische Klinik und Poliklinik I, Klinikum Großhadern, LMU Munich, Munich, Germany (R.H., C.K.); and DZHK, Partner Site Munich Heart Alliance, Munich, Germany (R.H., C.K., C.W., O.S.).
Renske de JongFrom 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-Maastricht, University Hospital RWTH Aachen, Aachen, Germany (J.G.); Medizinische Klinik und Poliklinik I, Klinikum Großhadern, LMU Munich, Munich, Germany (R.H., C.K.); and DZHK, Partner Site Munich Heart Alliance, Munich, Germany (R.H., C.K., C.W., O.S.).
Jan RossaintFrom 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-Maastricht, University Hospital RWTH Aachen, Aachen, Germany (J.G.); Medizinische Klinik und Poliklinik I, Klinikum Großhadern, LMU Munich, Munich, Germany (R.H., C.K.); and DZHK, Partner Site Munich Heart Alliance, Munich, Germany (R.H., C.K., C.W., O.S.).
Joana R ViolaFrom 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-Maastricht, University Hospital RWTH Aachen, Aachen, Germany (J.G.); Medizinische Klinik und Poliklinik I, Klinikum Großhadern, LMU Munich, Munich, Germany (R.H., C.K.); and DZHK, Partner Site Munich Heart Alliance, Munich, Germany (R.H., C.K., C.W., O.S.).
Giovanna LeoniFrom 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-Maastricht, University Hospital RWTH Aachen, Aachen, Germany (J.G.); Medizinische Klinik und Poliklinik I, Klinikum Großhadern, LMU Munich, Munich, Germany (R.H., C.K.); and DZHK, Partner Site Munich Heart Alliance, Munich, Germany (R.H., C.K., C.W., O.S.).
Ji Ming WangFrom 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-Maastricht, University Hospital RWTH Aachen, Aachen, Germany (J.G.); Medizinische Klinik und Poliklinik I, Klinikum Großhadern, LMU Munich, Munich, Germany (R.H., C.K.); and DZHK, Partner Site Munich Heart Alliance, Munich, Germany (R.H., C.K., C.W., O.S.).
Jochen GrommesFrom 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-Maastricht, University Hospital RWTH Aachen, Aachen, Germany (J.G.); Medizinische Klinik und Poliklinik I, Klinikum Großhadern, LMU Munich, Munich, Germany (R.H., C.K.); and DZHK, Partner Site Munich Heart Alliance, Munich, Germany (R.H., C.K., C.W., O.S.).
Rabea HinkelFrom 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-Maastricht, University Hospital RWTH Aachen, Aachen, Germany (J.G.); Medizinische Klinik und Poliklinik I, Klinikum Großhadern, LMU Munich, Munich, Germany (R.H., C.K.); and DZHK, Partner Site Munich Heart Alliance, Munich, Germany (R.H., C.K., C.W., O.S.).
Christian KupattFrom 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-Maastricht, University Hospital RWTH Aachen, Aachen, Germany (J.G.); Medizinische Klinik und Poliklinik I, Klinikum Großhadern, LMU Munich, Munich, Germany (R.H., C.K.); and DZHK, Partner Site Munich Heart Alliance, Munich, Germany (R.H., C.K., C.W., O.S.).
Christian WeberFrom 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-Maastricht, University Hospital RWTH Aachen, Aachen, Germany (J.G.); Medizinische Klinik und Poliklinik I, Klinikum Großhadern, LMU Munich, Munich, Germany (R.H., C.K.); and DZHK, Partner Site Munich Heart Alliance, Munich, Germany (R.H., C.K., C.W., O.S.).
Yvonne DöringFrom 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-Maastricht, University Hospital RWTH Aachen, Aachen, Germany (J.G.); Medizinische Klinik und Poliklinik I, Klinikum Großhadern, LMU Munich, Munich, Germany (R.H., C.K.); and DZHK, Partner Site Munich Heart Alliance, Munich, Germany (R.H., C.K., C.W., O.S.).
Alexander ZarbockFrom 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-Maastricht, University Hospital RWTH Aachen, Aachen, Germany (J.G.); Medizinische Klinik und Poliklinik I, Klinikum Großhadern, LMU Munich, Munich, Germany (R.H., C.K.); and DZHK, Partner Site Munich Heart Alliance, Munich, Germany (R.H., C.K., C.W., O.S.).
Oliver SoehnleinFrom 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-Maastricht, University Hospital RWTH Aachen, Aachen, Germany (J.G.); Medizinische Klinik und Poliklinik I, Klinikum Großhadern, LMU Munich, Munich, Germany (R.H., C.K.); and DZHK, Partner Site Munich Heart Alliance, Munich, Germany (R.H., C.K., C.W., O.S.). oliver.soehnlein@gmail.com.
Maastricht University Medical Centre · NL
Funding
The Role of Cellular Receptors Involved in Inflammation and Tumor ProgressionZIABC010015 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WANG, JI MING · 2009 to 2023
$6.3MThe Role of Cellular Receptors Involved in Inflammation and Tumor ProgressionZ01BC010015 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WANG, JI MING · 1996 to 2008
$944kIntramural NIH HHS Z01 BC010015
Abstract
rationaleChemokine-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.
objectiveBecause of the ambivalence of FPR2 ligands, we here investigate the role of FPR2 and its resolving ligand annexin A1 in atherogenesis. METHODS AND
resultsDeletion 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.
conclusionsInstructing 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.
Indexed as
AnimalsAnnexin A1Aortic DiseasesApolipoproteins EAtherosclerosisChemokine CCL2Chemokine CCL5Chemokine CXCL1ChemotaxisDietary FatsMiceMice, Inbred C57BLMice, KnockoutMyeloid CellsPeptidesrap1 GTP-Binding ProteinsAnnexin A1annexin A1, mouseannexin A1 peptide (2-26)Apolipoproteins ECcl2 protein, mouseCcl5 protein, mouseCcr2 protein, mouseCCR5 protein, mouseChemokine CCL2Chemokine CCL5Chemokine CXCL1Cxcl1 protein, mouseDietary Fatsformyl peptide receptor 2, mousePeptidesrap1 GTP-Binding ProteinsReceptors, CCR2Receptors, CCR5Receptors, Formyl PeptideReceptors, Interleukin-8Bannexin A1atherosclerosischemokineleukocytes
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