title: Anti-Apolipoprotein A-1 auto-antibodies are active mediators of atherosclerotic plaque vulnerability.
abstract: OBJECTIVE
  Anti-Apolipoprotein A-1 auto-antibodies (anti-ApoA-1 IgG) represent an emerging prognostic cardiovascular marker in patients with myocardial infarction or autoimmune diseases associated with high cardiovascular risk. The potential relationship between anti-ApoA-1 IgG and plaque vulnerability remains elusive. Thus, we aimed to investigate the role of anti-ApoA-1 IgG in plaque vulnerability.
  
  
  RESULTS
  Potential relationship between anti-ApoA-1 IgG and features of cardiovascular vulnerability was explored both in vivo and in vitro. In vivo, we investigated anti-ApoA-1 IgG in patients with severe carotid stenosis (n = 102) and in ApoE-/- mice infused with polyclonal anti-ApoA-1 IgG. In vitro, anti-ApoA-1 IgG effects were assessed on human primary macrophages, monocytes, and neutrophils. Intraplaque collagen was decreased, while neutrophil and matrix metalloprotease (MMP)-9 content were increased in anti-ApoA-1 IgG-positive patients and anti-ApoA-1 IgG-treated mice when compared with corresponding controls. In mouse aortic roots (but not in abdominal aortas), treatment with anti-ApoA-1 IgG was associated with increased lesion size when compared with controls. In humans, serum anti-ApoA-1 IgG levels positively correlated with intraplaque macrophage, neutrophil, and MMP-9 content, and inversely with collagen. In vitro, anti-ApoA-1 IgG increased macrophage release of CCL2, CXCL8, and MMP-9, as well as neutrophil migration towards TNF-α or CXCL8.
  
  
  CONCLUSIONS
  These results suggest that anti-ApoA-1 IgG might be associated with increased atherosclerotic plaque vulnerability in humans and mice.
authors.affiliation: Division of Cardiology, Faculty of Medicine, Foundation for Medical Researches, Geneva University Hospitals, Geneva, Switzerland. fabrizio.montecucco@unige.ch
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Montecucco
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vuilleumier
authors.forename: Sabrina
authors.initials: S
authors.lastname: Pagano
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lenglet
authors.forename: Maria
authors.initials: M
authors.lastname: Bertolotto
authors.forename: Vincent
authors.initials: V
authors.lastname: Braunersreuther
authors.forename: Graziano
authors.initials: G
authors.lastname: Pelli
authors.forename: Enikö
authors.initials: E
authors.lastname: Kovari
authors.forename: Bianca
authors.initials: B
authors.lastname: Pane
authors.forename: Giovanni
authors.initials: G
authors.lastname: Spinella
authors.forename: Aldo
authors.initials: A
authors.lastname: Pende
authors.forename: Domenico
authors.initials: D
authors.lastname: Palombo
authors.forename: Franco
authors.initials: F
authors.lastname: Dallegri
authors.forename: François
authors.initials: F
authors.lastname: Mach
authors.forename: Pascale
authors.initials: P
authors.lastname: Roux-Lombard
mesh_terms: D000368:Aged; D000818:Animals; D016632:Apolipoprotein A-I / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002343:Carotid Artery, Internal; D016893:Carotid Stenosis / Q000276:immunology*; D015331:Cohort Studies; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D058226:Plaque, Atherosclerotic / Q000276:immunology*
chemical_list: D016632:Apolipoprotein A-I; D001323:Autoantibodies; D015415:Biomarkers; D016207:Cytokines; D007074:Immunoglobulin G; D003094:Collagen; D020780:Matrix Metalloproteinase 9