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IgG N-Glycosylation Is Altered in Coronary Artery Disease.

ABSTRACT: Coronary artery disease (CAD) is the most common cardiovascular disease (CVD), and previous studies have shown a significant association between N-glycosylation, a highly regulated posttranslational modification, and the development of atherosclerotic plaques. Our aim was to determine whether the N-glycome of immunoglobulin G (IgG) is associated with CAD, as N-glycans are known to alter the effector functions of IgG, which may enhance the inflammatory response in CAD. Therefore, in this study, we isolated IgG from subjects with coronary atherosclerosis (CAD+) and from subjects with clean coronaries (CAD-). The purified IgGs were denatured and enzymatically deglycosylated, and the released and fluorescently labelled N-glycans were analysed by ultra-high performance liquid chromatography based on hydrophilic interactions with fluorescence detection (HILIC-UHPLC-FLR). Sex-stratified analysis of 316 CAD- and 156 CAD+ cases revealed differences in IgG N-glycome composition. The most notable differences were observed in women, where the presence of sialylated N-glycan structures was negatively associated with CAD. The obtained chromatograms provide insight into the IgG N-glycome composition in CAD as well as the biomarker potential of IgG N-glycans in CAD.

SUBMITTER: Radovani B

PROVIDER: S-EPMC9953309 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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IgG N-Glycosylation Is Altered in Coronary Artery Disease.

Radovani Barbara B Vučković Frano F Maggioni Aldo P AP Ferrannini Ele E Lauc Gordan G Gudelj Ivan I

Biomolecules 20230216 2

Coronary artery disease (CAD) is the most common cardiovascular disease (CVD), and previous studies have shown a significant association between N-glycosylation, a highly regulated posttranslational modification, and the development of atherosclerotic plaques. Our aim was to determine whether the N-glycome of immunoglobulin G (IgG) is associated with CAD, as N-glycans are known to alter the effector functions of IgG, which may enhance the inflammatory response in CAD. Therefore, in this study, w ...[more]

PMID: 36830744

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Project description:BackgroundInflammation plays a key role in the progression of atherosclerotic plaque for peripheral artery disease (PAD). Immunoglobulin G (IgG) glycosylation could modulate immunological effector functions and has been explored as biomarkers for various diseases.MethodsLectin microarray was applied to analyze the expression profile of serum IgG glycosylation in patients with lower-extremity peripheral artery disease (LEPAD), carotid artery stenosis (CAS), abdominal aortic aneurysm (AAA), and healthy controls. Lectin blot was performed to validate the differences.ResultsSNA (Sambucus nigra agglutinin) binding (preferred sialic acid) was significantly higher in the LEPAD (3.21 ± 2.06) and AAA (3.34 ± 2.42) groups compared to the CAS (2.47 ± 1.45) group. Significantly higher binding levels of ConA (Concanavalin A) (preferred mannose) and PSA (Pisum sativum agglutinin) (preferred fucose) were also observed in LEPAD compared to CAS patients. Among LEPAD patients, a significant lower binding level of Black bean crude (preferred GalNAc) was present for dyslipidemia patients. A higher binding level of MNA-M (Morniga M agglutinin) (preferred Mannose) and Jacalin-AIA (Artocarpus integrifolia agglutinin) (preferred Galβ3GalNAc) was observed for Fontaine severe patients. Higher binding levels of PHA-E (Phaseolus vulgaris Erythroagglutinin) and PHA-L (Phaseolus vulgaris Leucoagglutinin) (preferred Galβ4GlcNAc) were observed for diabetic patients, and higher binding of ASA (Allium sativum agglutinin) (preferred Mannose) was present in patients with hypertension. The level of high-sensitivity C-reactive protein (hsCRP) was positively associated with LTL (Lotus tetragonolobus lectin) (r = 0.44), PSA (r = 0.44), LCA (Lens Culinaris agglutinin) (r = 0.39), SNA (r = 0.57), and CSA (Cytisus sscoparius agglutinin) (r = 0.56). For CAS, symptomatic patients had lower binding levels of AAL (Aleuria aurantia lectin) (preferred fucose) and IAA (Iberis amara agglutinin) (preferred GalNAc). Blood total cholesterol level was positively associated with SNA-I (r = 0.36) and SBA (Soybean agglutinin) (r = r = 0.35). Creatinine levels were positively associated with lectins including, but not limited to, MNA-M (r = 0.42), CSA (r = 0.45), GHA (Glechoma hederacea agglutinin) (r = 0.42), and MNA-G (Morniga G agglutinin) (r = 0.45).ConclusionLEPAD patients had increased IgG binding levels of SNA and ConA compared to CAS, which could provide potential diagnostic value. Fontaine severity was associated with Mannose-rich IgG N-glycan, while diabetic LEPAD correlated with bisecting GlcNAc. The levels of hsCRP and creatinine were positively associated with IgG fucosylation and galactosylation. Changes in IgG glycosylation may play important roles in PAD pathogenesis and progression.

Project description:Background and aimAtypical coronary artery disease (ACAD) is characterized by atypical angina pectoris or silent myocardial ischemia. However, conventional diagnostic techniques are insufficient to identify this subtype of coronary atherosclerotic pathology, and specific and sensitive markers for diagnosing ACAD are still currently lacking. The aim of the present study is to identify a novel serum microRNA (miRNA) expression profile of ACAD patients and evaluate its clinical diagnostic value.Patients and methods127 patients who were diagnosed with ACAD and 54 age-matched controls were enrolled in this study. An initial screen of miRNA expression was performed in serum samples from 35 patients and 20 controls using TaqMan Low Density Array. A stem-loop quantitative reverse-transcription PCR (RT-qPCR) assay was conducted in the training and validation sets to confirm the levels of the altered miRNAs in 122 patients with ACAD and 68 controls. In addition, the potential target genes of the altered miRNAs were predicted using bioinformatics methods.ResultsThe TaqMan low density array and RT-qPCR analysis identified four serum miRNAs including miR-487a, miR-502, miR-208 and miR-215 that were significantly increased, while one miRNA, miR-29b, that was significantly decreased in ACAD patients compared with normal controls (P<0.05). The area under the receiver-operating-characteristic (ROC) curve (AUC) for the combined 5 serum miRNAs were 0.850 (95% CI, 0.734-0.966, P<0.001) and 0.909 (95% CI, 0.858-0.960, P<0.001) for the training set and validation set, respectively. In addition, target gene prediction showed that these five altered miRNAs are involved in affecting various aspects of cardiac or vascular remodeling, especially in the pathway involving inflammation and fibrosis.ConclusionOur findings indicate that the five altered serum miRNAs could be novel non-invasive biomarkers for ACAD and may also represent potential therapeutic targets for atherosclerosis and myocardial ischemia.

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IgG N-Glycosylation Is Altered in Coronary Artery Disease.

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IgG N-Glycosylation Is Altered in Coronary Artery Disease.

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