The advantageous role of annexin A1 in cardiovascular disease

ABSTRACT The inflammatory response protects the human body against infection and injury. However, uncontrolled and unresolved inflammation can lead to tissue damage and chronic inflammatory diseases. Therefore, active resolution of inflammation is essential to restore tissue homeostasis. This review focuses on the pro-resolving molecule annexin A1 (ANXA1) and its derived peptides. Mechanisms instructed by ANXA1 are multidisciplinary and affect leukocytes as well as endothelial cells and tissue resident cells like macrophages and mast cells. ANXA1 has an outstanding role in limiting leukocyte recruitment and different aspects of ANXA1 as modulator of the leukocyte adhesion cascade are discussed here. Additionally, this review details the therapeutic relevance of ANXA1 and its derived peptides in cardiovascular diseases since atherosclerosis stands out as a chronic inflammatory disease with impaired resolution and continuous leukocyte recruitment.

[1]  D. Jin,et al.  A novel anti-inflammatory mechanism of high density lipoprotein through up-regulating annexin A1 in vascular endothelial cells. , 2016, Biochimica et biophysica acta.

[2]  D. Granger,et al.  Formyl-Peptide Receptor 2/3/Lipoxin A4 Receptor Regulates Neutrophil-Platelet Aggregation and Attenuates Cerebral Inflammation: Impact for Therapy in Cardiovascular Disease , 2016, Circulation.

[3]  P. Pelegrín,et al.  Macrophage activation and polarization modify P2X7 receptor secretome influencing the inflammatory process , 2016, Scientific Reports.

[4]  Mark D. Huffman,et al.  Heart Disease and Stroke Statistics—2016 Update: A Report From the American Heart Association , 2016, Circulation.

[5]  F. Dell’Accio,et al.  Neutrophil-derived microvesicles enter cartilage and protect the joint in inflammatory arthritis , 2015, Science Translational Medicine.

[6]  S. Watson,et al.  The role of platelets in the recruitment of leukocytes during vascular disease , 2015, Platelets.

[7]  Malte Kelm,et al.  Effects of Proprotein Convertase Subtilisin/Kexin Type 9 Antibodies in Adults With Hypercholesterolemia: A Systematic Review and Meta-analysis. , 2015, Annals of internal medicine.

[8]  C. Reutelingsperger,et al.  Pharmacological Treatment with Annexin A1 Reduces Atherosclerotic Plaque Burden in LDLR-/- Mice on Western Type Diet , 2015, PloS one.

[9]  Oliver Soehnlein,et al.  Atherosclerosis - A matter of unresolved inflammation. , 2015, Seminars in immunology.

[10]  C. Gil,et al.  Targeting formyl peptide receptor 2 reduces leukocyte‐endothelial interactions in a murine model of stroke , 2015, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[11]  O. Farokhzad,et al.  Annexin A1-containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair. , 2015, The Journal of clinical investigation.

[12]  C. Weber,et al.  Annexin A1 counteracts chemokine-induced arterial myeloid cell recruitment. , 2015, Circulation research.

[13]  O. Farokhzad,et al.  Targeted nanoparticles containing the proresolving peptide Ac2-26 protect against advanced atherosclerosis in hypercholesterolemic mice , 2015, Science Translational Medicine.

[14]  P. Kovanen,et al.  Mast Cells as Effectors in Atherosclerosis , 2015, Arteriosclerosis, thrombosis, and vascular biology.

[15]  F. Swirski,et al.  Inflammation and repair in the ischaemic myocardium , 2014, Hämostaseologie.

[16]  D. Granger,et al.  Leukocyte-mediated tissue injury in ischemic stroke. , 2014, Current medicinal chemistry.

[17]  F. Ginhoux,et al.  Monocytes and macrophages: developmental pathways and tissue homeostasis , 2014, Nature Reviews Immunology.

[18]  E. Olson,et al.  Macrophages are required for neonatal heart regeneration. , 2014, The Journal of clinical investigation.

[19]  M. Perretti,et al.  Ligand-specific conformational change of the G-protein–coupled receptor ALX/FPR2 determines proresolving functional responses , 2013, Proceedings of the National Academy of Sciences.

[20]  K. Moore,et al.  Macrophages in atherosclerosis: a dynamic balance , 2013, Nature Reviews Immunology.

[21]  M. Perretti,et al.  Proresolving and Tissue-Protective Actions of Annexin A1–Based Cleavage-Resistant Peptides Are Mediated by Formyl Peptide Receptor 2/Lipoxin A4 Receptor , 2013, The Journal of Immunology.

[22]  M. Mayr,et al.  Heterogeneity in Neutrophil Microparticles Reveals Distinct Proteome and Functional Properties* , 2013, Molecular & Cellular Proteomics.

[23]  G. Dusting,et al.  Annexin Peptide Ac2-26 Suppresses TNFα-Induced Inflammatory Responses via Inhibition of Rac1-Dependent NADPH Oxidase in Human Endothelial Cells , 2013, PloS one.

[24]  Oliver Soehnlein,et al.  Resolution of inflammation: an integrated view , 2013, EMBO molecular medicine.

[25]  O. Soehnlein,et al.  The Complexity of Arterial Classical Monocyte Recruitment , 2013, Journal of Innate Immunity.

[26]  R. Flower,et al.  Anti-Allergic Cromones Inhibit Histamine and Eicosanoid Release from Activated Human and Murine Mast Cells by Releasing Annexin A1 , 2013, PloS one.

[27]  M. Nahrendorf,et al.  Leukocyte Behavior in Atherosclerosis, Myocardial Infarction, and Heart Failure , 2013, Science.

[28]  C. Reutelingsperger,et al.  Annexin A1, formyl peptide receptor, and NOX1 orchestrate epithelial repair. , 2013, The Journal of clinical investigation.

[29]  E. Morand,et al.  Reperfusion‐induced myocardial dysfunction is prevented by endogenous annexin‐A1 and its N‐terminal‐derived peptide Ac‐ANX‐A12‐26 , 2013, British journal of pharmacology.

[30]  Paul M Holloway,et al.  Leukocyte recruitment in the brain in sepsis: involvement of the annexin 1‐FPR2/ALX anti‐inflammatory system , 2012, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[31]  C. Weber,et al.  Lack of Neutrophil-Derived CRAMP Reduces Atherosclerosis in Mice , 2012, Circulation research.

[32]  Oliver Soehnlein,et al.  Multiple roles for neutrophils in atherosclerosis. , 2012, Circulation research.

[33]  S. Stevanović,et al.  Cleavage of Annexin A1 by ADAM10 during Secondary Necrosis Generates a Monocytic “Find-Me” Signal , 2012, The Journal of Immunology.

[34]  M. Perretti,et al.  Annexin A1 N-Terminal Derived Peptide Ac2-26 Exerts Chemokinetic Effects on Human Neutrophils , 2011, Front. Pharmacol..

[35]  P. Kubes,et al.  The neutrophil in vascular inflammation , 2011, Nature Medicine.

[36]  T. Eckle,et al.  Ischemia and reperfusion—from mechanism to translation , 2011, Nature Medicine.

[37]  D. Ye,et al.  Pleiotropic regulation of macrophage polarization and tumorigenesis by formyl peptide receptor-2 , 2011, Oncogene.

[38]  M. Szyper-Kravitz,et al.  [The dilemma regarding treatment of pulmonary embolism among elderly patients]. , 2011, Harefuah.

[39]  S. Butz,et al.  GDF-15 is an inhibitor of leukocyte integrin activation required for survival after myocardial infarction in mice , 2011, Nature Medicine.

[40]  M. Perretti,et al.  Evidence for an Anti-Inflammatory Loop Centered on Polymorphonuclear Leukocyte Formyl Peptide Receptor 2/Lipoxin A4 Receptor and Operative in the Inflamed Microvasculature , 2011, The Journal of Immunology.

[41]  B. Cheuk,et al.  Annexin A1 expression in atherosclerotic carotid plaques and its relationship with plaque characteristics. , 2011, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[42]  Oliver Soehnlein,et al.  Hyperlipidemia-Triggered Neutrophilia Promotes Early Atherosclerosis , 2010, Circulation.

[43]  P. Kubes,et al.  Intravascular Danger Signals Guide Neutrophils to Sites of Sterile Inflammation , 2010, Science.

[44]  P. Deb,et al.  Pathophysiologic mechanisms of acute ischemic stroke: An overview with emphasis on therapeutic significance beyond thrombolysis. , 2010, Pathophysiology : the official journal of the International Society for Pathophysiology.

[45]  R. Hannon,et al.  Anti-Inflammatory Role of the Murine Formyl-Peptide Receptor 2: Ligand-Specific Effects on Leukocyte Responses and Experimental Inflammation , 2010, The Journal of Immunology.

[46]  W. Junger,et al.  Circulating Mitochondrial DAMPs Cause Inflammatory Responses to Injury , 2009, Nature.

[47]  Marc Parmentier,et al.  International Union of Basic and Clinical Pharmacology. LXXIII. Nomenclature for the Formyl Peptide Receptor (FPR) Family , 2009, Pharmacological Reviews.

[48]  E. Chavakis,et al.  Del-1, an Endogenous Leukocyte-Endothelial Adhesion Inhibitor, Limits Inflammatory Cell Recruitment , 2008, Science.

[49]  M. Perretti,et al.  Fluctuation of annexin-A1 positive mast cells in chronic granulomatous inflammation , 2008, Inflammation Research.

[50]  M. Perretti,et al.  Annexin 1 mediates the rapid anti-inflammatory effects of neutrophil-derived microparticles. , 2008, Blood.

[51]  P. Libby,et al.  The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions , 2007, The Journal of experimental medicine.

[52]  F. D’Acquisto,et al.  Annexin 1 Cleavage in Activated Neutrophils , 2007, Journal of Biological Chemistry.

[53]  M. Cybulsky,et al.  Getting to the site of inflammation: the leukocyte adhesion cascade updated , 2007, Nature Reviews Immunology.

[54]  C. Serhan,et al.  Aspirin-Triggered Lipoxins Override the Apoptosis-Delaying Action of Serum Amyloid A in Human Neutrophils: A Novel Mechanism for Resolution of Inflammation1 , 2007, The Journal of Immunology.

[55]  M. Perretti,et al.  Activation of the annexin 1 counter‐regulatory circuit affords protection in the mouse brain microcirculation , 2007, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[56]  J. Eng,et al.  Proteomics Analysis of Human Coronary Atherosclerotic Plaque , 2007, Molecular & Cellular Proteomics.

[57]  G. Cagney,et al.  Annexin-1 and Peptide Derivatives Are Released by Apoptotic Cells and Stimulate Phagocytosis of Apoptotic Neutrophils by Macrophages1 , 2007, The Journal of Immunology.

[58]  U. Rescher,et al.  Proteolytic cleavage of annexin 1 by human leukocyte elastase. , 2006, Biochimica et biophysica acta.

[59]  Takao Shimizu,et al.  The Lipoxin Receptor ALX: Potent Ligand-Specific and Stereoselective Actions in Vivo , 2006, Pharmacological Reviews.

[60]  H. Christian,et al.  Post‐translational modification plays an essential role in the translocation of annexin A1 from the cytoplasm to the cell surface , 2006, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[61]  M. Perretti,et al.  Annexin 1 and its bioactive peptide inhibit neutrophil-endothelium interactions under flow: indication of distinct receptor involvement. , 2006, Blood.

[62]  M. Perretti,et al.  Annexin 1‐deficient neutrophils exhibit enhanced transmigration in vivo and increased responsiveness in vitro , 2005, Journal of leukocyte biology.

[63]  R. Ritchie,et al.  Annexin‐1 peptide Anx‐12–26 protects adult rat cardiac myocytes from cellular injury induced by simulated ischaemia , 2005, British journal of pharmacology.

[64]  S. Moss,et al.  Annexins: linking Ca2+ signalling to membrane dynamics , 2005, Nature Reviews Molecular Cell Biology.

[65]  M. Perretti,et al.  A Novel Effect for Annexin 1-Derived Peptide Ac2-26: Reduction of Allergic Inflammation in the Rat , 2005, Journal of Pharmacology and Experimental Therapeutics.

[66]  M. Perretti,et al.  Modulation of Phagocytosis of Apoptotic Neutrophils by Supernatant from Dexamethasone-Treated Macrophages and Annexin-Derived Peptide Ac2–261 , 2005, The Journal of Immunology.

[67]  M. Perretti,et al.  Formyl‐peptide receptor is not involved in the protection afforded by annexin 1 in murine acute myocardial infarct , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[68]  U. Rescher,et al.  An Annexin 1 N-Terminal Peptide Activates Leukocytes by Triggering Different Members of the Formyl Peptide Receptor Family1 , 2004, The Journal of Immunology.

[69]  F. Pons,et al.  Mediation of annexin 1 secretion by a probenecid-sensitive ABC-transporter in rat inflamed mucosa. , 2004, Biochemical pharmacology.

[70]  S. Feo,et al.  Anti-inflammatory effects of annexin-1: stimulation of IL-10 release and inhibition of nitric oxide synthesis. , 2003, International immunopharmacology.

[71]  J. Levine,et al.  Dexamethasone enhances interaction of endogenous Annexin 1 with L‐selectin and triggers shedding of L‐selectin in the monocytic cell line U‐937 , 2003, British journal of pharmacology.

[72]  S. Marullo,et al.  A novel calcium‐dependent proapoptotic effect of annexin 1 on human neutrophils , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[73]  M. Perretti,et al.  Leukocyte antiadhesive actions of annexin 1: ALXR- and FPR-related anti-inflammatory mechanisms. , 2003, Blood.

[74]  Swathi Arur,et al.  Annexin I is an endogenous ligand that mediates apoptotic cell engulfment. , 2003, Developmental cell.

[75]  A. Rosengarth,et al.  A calcium-driven conformational switch of the N-terminal and core domains of annexin A1. , 2003, Journal of molecular biology.

[76]  H. Christian,et al.  Evidence for a role of the adenosine 5'-triphosphate-binding cassette transporter A1 in the externalization of annexin I from pituitary folliculo-stellate cells. , 2003, Endocrinology.

[77]  M. Paul-Clark,et al.  The FASEB Journal express article 10.1096/fj.02-0239fje. Published online December 3, 2002. Aberrant inflammation and resistance to glucocorticoids in Annexin 1 –/ – Mouse , 2022 .

[78]  S. Marullo,et al.  Endogenous lipid- and peptide-derived anti-inflammatory pathways generated with glucocorticoid and aspirin treatment activate the lipoxin A4 receptor , 2002, Nature Medicine.

[79]  K. Ley,et al.  Deposition of Platelet RANTES Triggering Monocyte Recruitment Requires P-Selectin and Is Involved in Neointima Formation After Arterial Injury , 2002, Circulation.

[80]  K. Becker.  Anti-leukocyte Antibodies: LeukArrest (Hu23F2G) and Enlimomab (R6.5) in Acute Stroke , 2002, Current medical research and opinion.

[81]  Enlimomab Acute Stroke Trial Investigators.  Use of anti-ICAM-1 therapy in ischemic stroke , 2001, Neurology.

[82]  M. Perretti,et al.  Annexin 1 peptides protect against experimental myocardial ischemia‐reperfusion: analysis of their mechanism of action , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[83]  M. Perretti,et al.  Involvement of the receptor for formylated peptides in the in vivo anti-migratory actions of annexin 1 and its mimetics. , 2001, The American journal of pathology.

[84]  S. Rosen,et al.  A Potential Role for Annexin 1 as a Physiologic Mediator of Glucocorticoid-Induced L-Selectin Shedding from Myeloid Cells1 , 2001, The Journal of Immunology.

[85]  M. Perretti,et al.  Lipocortin 1 reduces myocardial ischemia‐reperfusion injury by affecting local leukocyte recruitment , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[86]  S. Marullo,et al.  Annexin 1 Binds to U937 Monocytic Cells and Inhibits Their Adhesion to Microvascular Endothelium: Involvement of the α4β1 Integrin1 , 2000, The Journal of Immunology.

[87]  V. Gerke,et al.  A novel ligand of the formyl peptide receptor: annexin I regulates neutrophil extravasation by interacting with the FPR. , 2000, Molecular cell.

[88]  M. Perretti,et al.  ANNEXIN I IS STORED WITHIN GELATINASE GRANULES OF HUMAN NEUTROPHIL AND MOBILIZED ON THE CELL SURFACE UPON ADHESION BUT NOT PHAGOCYTOSIS , 2000, Cell biology international.

[89]  CHRISTINE ZOUKI,et al.  The anti‐inflammatory peptides, antiflammins, regulate the expression of adhesion molecules on human leukocytes and prevent neutrophil adhesion to endothelial cells , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[90]  P. Hutchinson,et al.  Inhibitory effect of annexin I on synovial inflammation in rat adjuvant arthritis. , 1999, Arthritis and rheumatism.

[91]  K. Williams,et al.  Atherosclerosis--an inflammatory disease. , 1999, The New England journal of medicine.

[92]  M. Perretti,et al.  Promoting detachment of neutrophils adherent to murine postcapillary venules to control inflammation: effect of lipocortin 1. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[93]  R. Flower,et al.  IL-6 stimulates annexin 1 expression and translocation and suggests a new biological role as class II acute phase protein. , 1998, Cytokine.

[94]  P. Hutchinson,et al.  Antiinflammatory Effect of Lipocortin 1 in Experimental Arthritis , 1997, Inflammation.

[95]  H. Eichler,et al.  Dexamethasone down‐regulates the expression of L‐selectin on the surface of neutrophils and lymphocytes in humans* , 1997, Clinical pharmacology and therapeutics.

[96]  M. Perretti,et al.  Inhibition of neutrophil and monocyte recruitment by endogenous and exogenous lipocortin 1 , 1997, British journal of pharmacology.

[97]  R. Hannon,et al.  Mobilizing lipocortin 1 in adherent human leukocytes downregulates their transmigration , 1996, Nature Medicine.

[98]  M. Perretti,et al.  Selective inhibition of neutrophil function by a peptide derived from lipocortin 1 N-terminus. , 1995, Biochemical pharmacology.

[99]  P. Hutchinson,et al.  Detection of intracellular lipocortin 1 in human leukocyte subsets. , 1995, Clinical immunology and immunopathology.

[100]  M. Perretti,et al.  Leukocyte transmigration, but not rolling or adhesion, is selectively inhibited by dexamethasone in the hamster post-capillary venule. Involvement of endogenous lipocortin 1. , 1995, Journal of immunology.

[101]  M. Perretti,et al.  Alteration of neutrophil trafficking by a lipocortin 1 N-terminus peptide. , 1995, European journal of pharmacology.

[102]  A. Ahluwalia,et al.  Lipocortin-1 fragments inhibit neutrophil accumulation and neutrophil-dependent edema in the mouse. A qualitative comparison with an anti-CD11b monoclonal antibody. , 1993, Journal of immunology.

[103]  F. Frey,et al.  Presence of lipocortins I and IV, but not II and VI, in human platelets , 1993, FEBS letters.

[104]  A. Ullrich,et al.  Annexin I is phosphorylated in the multivesicular body during the processing of the epidermal growth factor receptor , 1993, The Journal of cell biology.

[105]  J. Westwick,et al.  Evidence for the presence and location of annexins in human platelets. , 1992, Biochemical and biophysical research communications.

[106]  K. Nakanishi,et al.  Identification of immuno-reactive lipocortin 1-like molecules in serum and plasma by an enzyme immunoassay for lipocortin 1. , 1992, Biochimica et biophysica acta.

[107]  J. Römisch,et al.  Annexins I to VI: quantitative determination in different human cell types and in plasma after myocardial infarction , 1992, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[108]  J. Relton,et al.  Lipocortin-1 is an endogenous inhibitor of ischemic damage in the rat brain , 1991, The Journal of experimental medicine.

[109]  J. Fallon,et al.  Selective secretion of annexin 1, a protein without a signal sequence, by the human prostate gland. , 1991, The Journal of biological chemistry.

[110]  R. Flower,et al.  Hydrocortisone induces lipocortin 1 production by peripheral blood mononuclear cells in vivo in man. , 1990, Biochemical Society transactions.

[111]  H. Carp.  Mitochondrial N-formylmethionyl proteins as chemoattractants for neutrophils , 1982, The Journal of experimental medicine.

[112]  G. J. Blackwell,et al.  Anti-inflammatory steroids induce biosynthesis of a phospholipase A2 inhibitor which prevents prostaglandin generation , 1979, Nature.

[113]  J. Darnell,et al.  Mitochondrial protein synthesis in HeLa cells. , 1974, Journal of molecular biology.

[114]  P. Libby,et al.  From Lipids to Inflammation : New Approaches to Reducing Atherosclerotic Risk , 2016 .

[115]  A. Tall,et al.  The Success Story of LDL Cholesterol Lowering , 2016 .

[116]  E. Falk,et al.  Mechanisms of Plaque Formation and Rupture , 2014 .

[117]  T. Lehtimäki,et al.  Smooth muscle cells in human atherosclerosis: proteomic profiling reveals differences in expression of Annexin A1 and mitochondrial proteins in carotid disease. , 2013, Journal of molecular and cellular cardiology.

[118]  G. Hajishengallis,et al.  Endogenous modulators of inflammatory cell recruitment. , 2013, Trends in immunology.

[119]  M. Perretti,et al.  Functional and ultrastructural analysis of annexin A1 and its receptor in extravasating neutrophils during acute inflammation. , 2009, The American journal of pathology.

[120]  F. D’Acquisto,et al.  Annexin A1 and glucocorticoids as effectors of the resolution of inflammation , 2009, Nature Reviews Immunology.

[121]  M. Perretti,et al.  Cell localization of the anti-inflammatory protein annexin 1 during experimental inflammatory response. , 2001, Italian journal of anatomy and embryology = Archivio italiano di anatomia ed embriologia.

[122]  S. Marullo,et al.  Annexin 1 binds to U937 monocytic cells and inhibits their adhesion to microvascular endothelium: involvement of the alpha 4 beta 1 integrin. , 2000, Journal of immunology.