CD14 as a potential receptor and key regulator of anti-apolipoproteina-1 IgG-mediated positive chronotropic effect on cardiac cells

Anti-Apolipoprotein A-1 IgG Predict All-Cause Mortality and Are Associated with Fc Receptor-Like 3 Polymorphisms

“…Our findings raise the possibility that presence of anti-apoA-1 IgG leads to pathophysiological events affecting not only CV prognosis, but also survival in the long term. Based upon previous studies, such events could be related to a chronic low-grade inflammatory state through sustained activation of the TLR2/TLR4/CD14 complex and production of pro-inflammatory cytokines ( 14 , 18 , 21 , 24 , 38 ), associations with elevated high-sensitivity C-reactive protein and uric acid levels ( 23 , 25 ), impairment of HDL function ( 10 – 13 , 16 , 17 ), interference with basal heart rate regulation ( 22 , 24 , 25 ) or B-cell epitope spreading ( 39 ). Other pathophysiological mechanisms, other than those currently ascribed to anti-apoA-1 IgG could also be involved, in the same way that multiple molecular pathways underlie the associations of other autoantibodies with all-cause mortality in the community ( 7 , 9 , 40 , 41 ).…”

“…Subsequently, in vitro and animal studies demonstrated the ability of these autoantibodies to elicit a pro-inflammatory and pro-atherogenic response through interaction with the TLR2/TLR4/CD14 complex, followed by NF-κB and MAPK downstream activation as the main molecular pathway (18–24). …”

“…More than a decade ago, early clinical studies have supported the role of autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG), the principal component of high-density lipoproteins (HDLs), as mediators of chronic low-grade inflammation and predictors of unfavorable outcomes in patients with ADs ( 10 – 17 ). Subsequently, in vitro and animal studies demonstrated the ability of these autoantibodies to elicit a pro-inflammatory and pro-atherogenic response through interaction with the TLR2/TLR4/CD14 complex, followed by NF-κB and MAPK downstream activation as the main molecular pathway ( 18 – 24 ).…”