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A9.11 Anti-apolipoprotein A1 autoantibodies induce tissue factor activity and expression: a role in atherothrombosis
  1. Sabrina Pagano1,2,
  2. Julien Virzi1,2,
  3. Nathalie Satta1,2,
  4. Tiphaine Mannic1,2,
  5. Pascale Roux-Lombard1,3,
  6. François Mach4,
  7. Fabrizio Montecucco1,2,4,
  8. Nicolas Vuilleumier1,2
  1. 1Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, Switzerland
  2. 2Department of Human Protein Sciences, Faculty of Medicine, Geneva, Switzerland
  3. 3Division of Immunology and Allergy, Department of Internal Medicine, Geneva University Hospitals, Switzerland
  4. 4Division of Cardiology, Geneva University Hospitals, Faculty of Medicine, Foundation for Medical Researches, Geneva, Switzerland

Abstract

Introduction Autoimmune-mediated inflammation may play a role in atherosclerosis and atherothrombosis, essential features for cardiovascular disease (CVD) manifestations. Anti-Apolipoprotein A-1 (ApoA-1) IgG autoantibodies are an independent predictor of poor cardiovascular outcome in different clinical settings, promote inflammation and atherogenesis and are associated with increased atherosclerotic plaque vulnerability in humans and mice.

Aim To determine whether anti-ApoA-1 IgG are associated with Tissue Factor (TF) expression, a key regulator of the extrinsic coagulation pathway involved in atherothrombosis, responsible for the majority of acute CVD manifestations.

Methods Atherothrombosis features were explored in vivo by immunohistochemical TF staining on human carotid atherosclerotic plaques from (n = 102) patients with severe carotid stenosis and in vitro, on human monocyte derived macrophages (HMDM), TF expression and pro-coagulant activity detected by cytofluorimetry and chromogenic assay respectively.

Results In vivo atherosclerotic biopsies derived from patients with high circulating levels of anti-apoA-1 IgG (n = 20) displayed a higher TF expression when compared to biopsies from patients with low anti-apoA-1 IgG levels (9.3% vs 3.3%, p<0.0001). Spearman correlation reported a significant association between the circulating levels of those autoantibodies and TF expression (r = 0.41, p<0.001), as well as between CD68 atherosclerotic plaque expression and TF expression (r = 0.33, p = 0.004). On HMDM, anti-ApoA-1 IgG induced a significant dose-dependent increase in TF expression and a pro-coagulant activity only in supernatants and cells treated with anti-ApoA-1 IgG (p = 0.02, p<0.0001, p = 0.0006 respectively).

Conclusions We demonstrated that anti-ApoA-1 IgG are associated with higher propensity to atherothrombosis, the in vitro results suggest they could per se induce TF expression, supporting a possible causal link between anti-ApoA-1 IgG and atherothrombosis.

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