A9.11 Anti-apolipoprotein A1 autoantibodies induce tissue factor activity and expression: a role in atherothrombosis. (31st January 2014)

• Record Type: Journal Article
• Authors: Pagano, Sabrina; Virzi, Julien; Satta, Nathalie; Mannic, Tiphaine; Roux-Lombard, Pascale; Mach, François; Montecucco, Fabrizio; Vuilleumier, Nicolas
• Is Part Of: Annals of the rheumatic diseases. Volume 73:Supplement 1(2014)
• Page Start: A96
• Page End: A96
• Publication Date: 2014-01-31
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2013-205124.223
• Languages: English
• ISSNs: 0003-4967

Abstract

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.