Anti‐ApoA‐1 IgG serum levels predict worse poststroke outcomes

Carbone, Federico; Satta, Nathalie; Virzi, Julien; Burger, Fabienne; Roth, Aline; Roversi, Gloria; Tamborino, Carmine; Casetta, Ilaria; Seraceni, Silva; Trentini, Alessandro; Padroni, Marina; Dallegri, Franco; Lalive, Patrice H.; Mach, François; Fainardi, Enrico; Vuilleumier, Nicolas

doi:10.1111/eci.12664

Cited by 18 publications

(30 citation statements)

References 39 publications

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“…Among autoantibodies of interest in CVD, the interest in antibodies against apolipoprotein A-1 (anti-ApoA-1 IgG) appears to be gaining momentum. Indeed, three recent studies derived from a large multicenter general population cohort demonstrated that anti-ApoA-1 IgGs were an independent cardiovascular (CV) risk factor predictive of poor prognosis [3][4][5] similarly to what had been reported previously and more recently in high CV risk populations [6][7][8][9][10][11]. In parallel, translational studies pointed to these autoantibodies as mediators of atherogenesis, promoting atherosclerosis, myocardial necrosis, and mice death through toll-like receptors (TLR) 2,4 and CD14 signaling [12][13][14].…”

Section: Introductionsupporting

confidence: 73%

Anti-ApoA-1 IgGs in Familial Hypercholesterolemia Display Paradoxical Associations with Lipid Profile and Promote Foam Cell Formation

Pagano

Magenta

D'agostino

et al. 2019

JCM

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Aims: Anti-Apolipoprotein A-1 autoantibodies (anti-ApoA-1 IgG) promote atherogenesis via innate immune receptors, and may impair cellular cholesterol homeostasis (CH). We explored the presence of anti-ApoA-1 IgG in children (5–15 years old) with or without familial hypercholesterolemia (FH), analyzing their association with lipid profiles, and studied their in vitro effects on foam cell formation, gene regulation, and their functional impact on cholesterol passive diffusion (PD). Methods: Anti-ApoA-1 IgG and lipid profiles were measured on 29 FH and 25 healthy children. The impact of anti-ApoA-1 IgG on key CH regulators (SREBP2, HMGCR, LDL-R, ABCA1, and miR-33a) and foam cell formation detected by Oil Red O staining were assessed using human monocyte-derived macrophages. PD experiments were performed using a validated THP-1 macrophage model. Results: Prevalence of high anti-ApoA-1 IgG levels (seropositivity) was about 38% in both study groups. FH children seropositive for anti-ApoA-1 IgG had significant lower total cholesterol LDL and miR-33a levels than those who were seronegative. On macrophages, anti-ApoA-1 IgG induced foam cell formation in a toll-like receptor (TLR) 2/4-dependent manner, accompanied by NF-kB- and AP1-dependent increases of SREBP-2, LDL-R, and HMGCR. Despite increased ABCA1 and decreased mature miR-33a expression, the increased ACAT activity decreased membrane free cholesterol, functionally culminating to PD inhibition. Conclusions: Anti-ApoA-1 IgG seropositivity is frequent in children, unrelated to FH, and paradoxically associated with a favorable lipid profile. In vitro, anti-ApoA-1 IgG induced foam cell formation through a complex interplay between innate immune receptors and key cholesterol homeostasis regulators, functionally impairing the PD cholesterol efflux capacity of macrophages.

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Section: Introductionsupporting

confidence: 73%

Anti-ApoA-1 IgGs in Familial Hypercholesterolemia Display Paradoxical Associations with Lipid Profile and Promote Foam Cell Formation

Pagano

Magenta

D'agostino

et al. 2019

JCM

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“…These aspects are of utmost importance as we believe they represent the pathophysiological basis for most cardiovascular (CV) diseases, which remain the leading cause of death around the world. We agree with the concepts discussed in this review and would like to strengthen some of them based on our experience in the study of atherosclerosis 2‐5 …”

Section: Figuresupporting

confidence: 70%

Plaque vulnerability and adverse outcomes: The long road to fight atherosclerosis

Bonaventura

Liberale

Carbone

et al. 2020

Eur J Clin Investigation

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“…HCV GT3 is associated with a higher risk of early death and liver-related clinical events [26] and we have previously reported genotype-specific differences in regulation of lipoproteins [27]. Anti-ApoA-1 IgG serum levels have been found to predict worse post-stroke outcomes [28] and HCV is associated with increased cerebrovascular morbidity and mortality [2].…”

Section: Discussionmentioning

confidence: 99%

Autoantibody to apolipoprotein A-1 in hepatitis C virus infection: a role in atherosclerosis?

Bridge

Pagano²,

Jones

et al. 2018

Journal of Hepatology

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Background/purpose One to three per cent of the world's population has hepatitis C virus (HCV) infection, which is not only a major cause of liver disease and cancer but also associated with an increased risk of atherosclerosis, despite an ostensibly favourable lipid profile. Autoantibodies are frequent in HCV infection and emerging evidence shows that autoantibodies could be valuable for cardiovascular disease (CVD) risk stratification. This study investigated a novel independent biomarker of CVD, autoantibodies to apolipoprotein A-1 (anti-apoA-1 IgG) and lipids in patients with chronic HCV before, during and after direct-acting anti-viral (DAA) therapy. Methods Eighty-nine blinded serum samples from 27 patients with advanced chronic HCV were assayed for lipids and anti-apoA-1 IgG by ELISA. Results Pre-treatment HCV viral load correlated with high-density lipoprotein cholesterol (HDL-C, r = 0.417; p = 0.042) and negatively with apolipoprotein (apo)B (r =-0.497; p = 0.013) and markers of CVD risk, the apoB/apoA-1 ratio (r =-0.490; p = 0.015) and triglyceride level (TG)/HDL-C ratio (r =-0.450; p = 0.031). Fourteen (52%) of 27 patients had detectable anti-apoA-1 IgG autoantibodies pre-treatment; only two became undetectable with virological cure. Autoantibody-positive sera had lower apoA-1 (p = 0.012), HDL-C (p = 0.009) and total cholesterol (p = 0.006) levels. Conclusions This is the first report of the presence of an emerging biomarker for atherosclerosis, anti-apoA-1 IgG, in some patients with HCV infection. It may be induced by apoA-1 on the surface of HCV lipoviral particles. The autoantibodies inversely correlate with apoA-1 and HDL levels and may render HDL dysfunctional. Whether these hypothesis-generating findings have clinical implications in HCV patients requires further study.

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Anti‐ApoA‐1 IgG serum levels predict worse poststroke outcomes

Cited by 18 publications

References 39 publications

Anti-ApoA-1 IgGs in Familial Hypercholesterolemia Display Paradoxical Associations with Lipid Profile and Promote Foam Cell Formation

Anti-ApoA-1 IgGs in Familial Hypercholesterolemia Display Paradoxical Associations with Lipid Profile and Promote Foam Cell Formation

Plaque vulnerability and adverse outcomes: The long road to fight atherosclerosis

Autoantibody to apolipoprotein A-1 in hepatitis C virus infection: a role in atherosclerosis?

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