Oxidatively altered IgG with increased immunoreactivity to β2-glycoprotein I and its peptide clusters influence human coronary artery endothelial cells

Artenjak, Andrej; Omersel, Jasna; Grabnar, Pegi Ahlin; Mlinarič-Raščan, Irena; Shoenfeld, Yehuda; Sodin‐Šemrl, Snežna; Božič, Borut; Čučnik, Saša

doi:10.1177/0961203314561073

Cited by 7 publications

(4 citation statements)

References 35 publications

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“…Lin et al (24) have reported that in patients with inflammation, b2gpI levels were in negative correlation with CRP and in positive correlation with negative acute phase proteins (such as albumin and transferrin). It was reported that acute phase proteins (such as SAA) have been associated with the pathology of anti-b2gpI Abs and that SAA levels were increased and correlated with the history of thrombosis in APS patients (25), while in healthy young Japanese, no correlation between CRP and SAA levels was observed (26). In our study, hsCRP concentrations were significantly different between subjects with increased IgM aCL Abs titers and those without it.…”

Section: Discussioncontrasting

confidence: 57%

“…Antiphospholipid antibodies are regarded as natural autoantibodies and due to »molecular mimicry between microbial epitopes and human b2gpI it is possible that in genetically predisposed subjects, generation of aPL Abs might be initiated« (28). However, predisposing factors are not completely elucidated yet and there are several reports that suggest that pro-inflammatory cytokines and acute phase reactants (25) are important for generating »second hit« that is vital in the pathology of aPL Abs. Our study provides a rationale for the fact that correction of BMI and lipid status might be beneficial in reduction and/or elimination of predisposing factors that might trigger thrombotic events in otherwise healthy Serbian middle-aged subjects.…”

Section: Discussionmentioning

confidence: 99%

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Antiphospholipid antibodies in healthy Serbian middle-aged subjects: Preliminary data

Bećarevic¹,

Jovičić²,

Ignjatović³

et al. 2022

J Med Biochemistry

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Backgroud: The investigation of the prevalence of the IgG and the IgM isotypes of anticardiolipin (aCL) and anti-β2glycoprotein I (aβ2gpI) Abs in healthy Serbian middle-aged subjects was the main goal of our study. In addition, we analyzed the potential associations of above-mentioned Abs with serum proteins and lipids/lipoproteins. Methods: Forty healthy subjects were included in our study. Obesity (BMI ≥ 30 kg/m2) was present in 8/40 (20%) subjects. Titers of analyzed Abs were measured by ELISA. Results: The prevalence of IgG and IgM aβ2gpI Abs was 5% and 12.5%, respectively, while the prevalence of IgM aCL was 10%. The IgG aβ2gpI Abs were significantly different between subjects with normal triglycerides levels and those with hypertriglyceridemia (Mann-Whitney, P = 0.014). The significant difference in hsCRP concentrations was observed between subjects with the increased levels of the IgM isotype of aCL Abs and those with normal IgM aCL values (Mann-Whitney, P = 0.028). Conclusion: Dyslipidemia and BMI ≥30 were associated with aPL Abs and therefore, the correction of BMI and lipid status might be beneficial in reduction or elimination of predisposing factors that might trigger thrombotic events in otherwise healthy middle-aged subjects. Larger national study is necessary to confirm our findings.

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Section: Discussioncontrasting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Antiphospholipid antibodies in healthy Serbian middle-aged subjects: Preliminary data

Bećarevic¹,

Jovičić²,

Ignjatović³

et al. 2022

J Med Biochemistry

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“…That is why TNF α has not been included in the compilation of tested molecules, for example, IL-6, IL-8, PAI-1, and VCAM-1, in this study. TNF α itself had been previously tested as a single inducer of HCAEC and was shown to upregulate GRO α , IL-6, IL-8, and MCP-1 [ 79 ]. Consequently, it would be of further interest to determine the effects of drugs, such as anti-TNF α inhibitors, methotrexate, and steroids on TNF α -activated HCAEC.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Drug Effects on Primary Human Coronary Artery Endothelial Cells Activated by Serum Amyloid A

Lakota

Hrušovar

Ogrič

et al. 2018

Mediators of Inflammation

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Background RA patients have a higher incidence of cardiovascular diseases compared to the general population. Serum amyloid A (SAA) is an acute-phase protein, upregulated in sera of RA patients. Aim To determine the effects of medications on SAA-stimulated human coronary artery endothelial cells (HCAEC). Methods HCAEC were preincubated for 2 h with medications from sterile ampules (dexamethasone, methotrexate, certolizumab pegol, and etanercept), dissolved in medium (captopril) or DMSO (etoricoxib, rosiglitazone, meloxicam, fluvastatin, and diclofenac). Human recombinant apo-SAA was used to stimulate HCAEC at a final 1000 nM concentration for 24 hours. IL-6, IL-8, sVCAM-1, and PAI-1 were measured by ELISA. The number of viable cells was determined colorimetrically. Results SAA-stimulated levels of released IL-6, IL-8, and sVCAM-1 from HCAEC were significantly attenuated by methotrexate, fluvastatin, and etoricoxib. Both certolizumab pegol and etanercept significantly decreased PAI-1 by an average of 43%. Rosiglitazone significantly inhibited sVCAM-1 by 58%. Conclusion We observed marked influence of fluvastatin on lowering cytokine production in SAA-activated HCAEC. Methotrexate showed strong beneficial effects for lowering released Il-6, IL-8, and sVCAM-1. Interesting duality was observed for NSAIDs, with meloxicam exhibiting opposite-trend effects from diclofenac and etoricoxib. This represents unique insight into specific responsiveness of inflammatory-driven HCAEC relevant to atherosclerosis.

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“…Although aPL are persistent in APS patients, thrombosis occurs only occasionally, suggesting the involvement of other triggers that, together with aPL, turn the hemostatic balance in favor of thrombosis. In the development of APS, a two hit theory has been proposed in which the continuous presence of aPL as the first hit and inflammation, trauma, or surgery as a second hit together lead to thrombus formation [66,67]. APS pathogenesis clearly involves both inflammatory and coagulation pathways in endothelial cells, monocytes, neutrophils, and platelets.…”

Section: Pathological Mechanisms Of the Antiphospholipid Syndromementioning

confidence: 99%

Extracellular Vesicles: Intercellular Communication Mediators in Antiphospholipid Syndrome

Štok¹,

Čučnik²,

Sodin‐Šemrl³

et al. 2022

Antiphospholipid Syndrome - Recent Advances in Clinical and Basic Aspects

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Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis, obstetric complications and the presence of antiphospholipid antibodies (aPL) that cause endothelial injury and thrombophilia. Extracellular vesicles are involved in endothelial and thrombotic pathologies and may therefore have an influence on the prothrombotic status of APS patients. Intercellular communication and connectivity are important mechanisms of interaction between healthy and pathologically altered cells. Despite well-characterized in vitro and in vivo models of APS pathology, the field of extracellular vesicles is still largely unexplored and could therefore provide an insight into the APS mechanism and possibly serve as a biomarker to identify patients at increased risk. The analysis of EVs poses a challenge due to the lack of standardized technology for their isolation and characterization. Recent findings in the field of EVs offer promising aspects that may explain their role in the pathogenesis of various diseases, including APS.

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Oxidatively altered IgG with increased immunoreactivity to β2-glycoprotein I and its peptide clusters influence human coronary artery endothelial cells

Cited by 7 publications

References 35 publications

Antiphospholipid antibodies in healthy Serbian middle-aged subjects: Preliminary data

Antiphospholipid antibodies in healthy Serbian middle-aged subjects: Preliminary data

Analysis of Drug Effects on Primary Human Coronary Artery Endothelial Cells Activated by Serum Amyloid A

Extracellular Vesicles: Intercellular Communication Mediators in Antiphospholipid Syndrome

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