UNIGE document Scientific Article
previous document  unige:85041  next document
add to browser collection

Anti-apolipoprotein A-1 auto-antibodies as active modulators of atherothrombosis

Bertolotto, Maria
Pane, Bianca
Spinella, Giovanni
Palombo, Domenico
show hidden authors show all authors [1 - 16]
Published in Thrombosis and haemostasis. 2016, vol. 116, no. 3
Abstract Humoral autoimmune-mediated inflammation plays a role in atherogenesis, and potentially in arterial thrombosis. Anti-apolipoprotein A-1 (apoA-1) IgG have been reported to represent emergent mediators of atherogenesis through Toll-like receptors (TLR) 2, 4 and CD14 signalling. We investigated the role of anti-apoA-1 IgG on tissue factor (TF) expression and activation, a key coagulation regulator underlying atherothrombosis. Atherothrombosis features were determined by immunohistochemical TF staining of human carotid biopsies derived from patients with severe carotid stenosis undergoing elective surgery (n=176), and on aortic roots of different genetic backgrounds mice (ApoE-/-; TLR2-/-ApoE-/- and TLR4-/-ApoE-/-) exposed to passive immunisation with anti-apoA-1 IgG. Human serum levels of anti-apoA-1 IgG were measured by ELISA. In vitro, on human-monocyte-derived-macrophages (HMDM) the anti-apoA-1 IgG increased TF expression and activity were analysed by FACS and chromogenic assays in presence of different pharmacological inhibitors. Human serum anti-apoA-1 IgG levels significantly correlated to intraplaque TF expression in carotid biopsies (r=0.31, p<0.001), which was predictive of clinically symptomatic lesions. On HMDM, anti-apoA-1 IgG induced a TLR2, 4/CD14-dependent increase in TF expression and activity, involving NF-kappaB and a c-Jun N-terminal kinase-dependent AP-1 transcription factors. In ApoE-/- mice, anti-apoA-1 IgG passive immunisation significantly enhanced intraplaque TF expression when compared to control IgG. This effect was lost in both TLR2-/-ApoE-/- and TLR4-/-ApoE-/- backgrounds. These results demonstrate that anti-apoA-1 IgG are associated with TF expression in human atherosclerotic plaques, induce TF expression in vitro and in vivo through TLR2 and 4 signalling, supporting a possible causal relationship between anti-apoA-1 IgG and atherothrombosis.
PMID: 27356567
Full text
Article (Published version) (562 Kb) - public document Free access
Research groups Chimie et protéomique clinique (270)
Geneva Platelet Group (13)
L'athérosclérose et ses complications cliniques (591)
Traits génétiques complexes (901)
(ISO format)
PAGANO, Sabrina et al. Anti-apolipoprotein A-1 auto-antibodies as active modulators of atherothrombosis. In: Thrombosis and haemostasis, 2016, vol. 116, n° 3. doi: 10.1160/TH16-03-0229 https://archive-ouverte.unige.ch/unige:85041

590 hits



Deposited on : 2016-07-05

Export document
Format :
Citation style :