Glycosylation of human plasma lipoproteins reveals a high level of diversity, which directly impacts their functional properties

Sukhorukov, Vasily N.; Gudelj, Ivan; Pučić‐Baković, Maja; Zakiev, Emile; Orekhov, Alexander N.; Kontush, Anatol; Lauc, Gordan

doi:10.1016/j.bbalip.2019.01.005

Cited by 26 publications

(26 citation statements)

References 67 publications

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“…The glycosylated forms of apolipoprotein A-I (the main protein component of serum HDL) were found to increase with the time course of acute myocardial infarction, suggesting that the glycosylation of apolipoprotein A-I might be associated with this protein's cholesterol-clearance and anti-atherosclerosis effects [ 31 ]. In addition, the removal of glycan terminal sialic acid (desialylation) from LDL has been shown to accelerate the uptake and accumulation of LDL in THP-1 cells and to significantly reduce the ability of HDL to clear cholesterol esters in THP-1 cells [ 32 ].…”

Section: Resultsmentioning

confidence: 99%

A puzzle piece of protein N-glycosylation in chicken egg: N-glycoproteome of chicken egg vitelline membrane

Xiao

Wang

Cheng

et al. 2020

International Journal of Biological Macromolecules

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The chicken egg vitelline membrane (CEVM) is an important structure for the transmembrane transport of egg yolk components, protection of the blastodisc, and separation of egg white and egg yolk. In this study, the N-glycoproteome of the CEVM was mapped and analyzed in depth. Total protein of the CEVM was digested, and the glycopeptides were enriched by a hydrophilic interaction liquid chromatography microcolumn and identified by nano liquid chromatography/tandem mass spectrometry. A total of 435 N-glycosylation sites on 208 N-glycoproteins were identified in CEVM. Gene Ontology enrichment analysis showed that CEVM N-glycoproteins are mainly involved in the regulation of proteinases/inhibitors and transmembrane transport of lipids. Mucin-5B is the primary N-glycoprotein in the CEVM. Comparison of the main N-glycoproteins between the CEVM and other egg parts revealed the tissue specificity of N-glycosylation of egg proteins. The results provide insights into protein N-glycosylation in the chicken egg, CEVM functions and underlying mechanisms.

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Section: Resultsmentioning

confidence: 99%

A puzzle piece of protein N-glycosylation in chicken egg: N-glycoproteome of chicken egg vitelline membrane

Xiao

Wang

Cheng

et al. 2020

International Journal of Biological Macromolecules

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“…Importantly, altered glycosylation of plasma proteins affects their function. A recent study, for example, showed that incomplete glycosylation of lipoproteins leads to accumulation of cholesterol in cells (34). Prospective human studies with integrated glycomics and glycoproteomics data will be able to address the interaction between protein concentration and glycosylation patterns in relation to disease risk and are thus highly warranted.…”

Section: Discussionmentioning

confidence: 99%

Plasma N-Glycans as Emerging Biomarkers of Cardiometabolic Risk: A Prospective Investigation in the EPIC-Potsdam Cohort Study

et al. 2020

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Plasma protein N-glycan profiling integrates information on enzymatic protein glycosylation, which is a highly controlled ubiquitous posttranslational modification. Here we investigate the ability of the plasma N-glycome to predict incidence of type 2 diabetes and cardiovascular diseases (CVDs; i.e., myocardial infarction and stroke). RESEARCH DESIGN AND METHODSBased on the prospective European Prospective Investigation of Cancer (EPIC)-Potsdam cohort (n 5 27,548), we constructed case-cohorts including a random subsample of 2,500 participants and all physician-verified incident cases of type 2 diabetes (n 5 820; median follow-up time 6.5 years) and CVD (n 5 508; median follow-up time 8.2 years). Information on the relative abundance of 39 N-glycan groups in baseline plasma samples was generated by chromatographic profiling. We selected predictive N-glycans for type 2 diabetes and CVD separately, based on cross-validated machine learning, nonlinear model building, and construction of weighted prediction scores. This workflow for CVD was applied separately in men and women. RESULTSThe N-glycan-based type 2 diabetes score was strongly predictive for diabetes risk in an internal validation cohort (weighted C-index 0.83, 95% CI 0.78-0.88), and this finding was externally validated in the Finland Cardiovascular Risk Study (FINRISK) cohort. N-glycans were moderately predictive for CVD incidence (weighted Cindices 0.66, 95% CI 0.60-0.72, for men; 0.64, 95% CI 0.55-0.73, for women). Information on the selected N-glycans improved the accuracy of established and clinically applied risk prediction scores for type 2 diabetes and CVD. CONCLUSIONSSelected N-glycans improve type 2 diabetes and CVD prediction beyond established risk markers. Plasma protein N-glycan profiling may thus be useful for risk stratification in the context of precisely targeted primary prevention of cardiometabolic diseases.

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“…Clear attenuation in cholesterol egress via PLY-NanA treated HDL2 was demonstrated. The additional effect of NanA in the reduced cholesterol efflux was expected as glycosylation has been shown to directly affect the functional properties of HDL (Sukhorukov et al, 2019) (Figure 4C).…”

Section: Ply and Nana Convert Hdl From Anti-inflammatory To Pro-inflammatory And Pro-atherogenic Particlesmentioning

confidence: 86%

Streptococcus pneumoniae pneumolysin and neuraminidase A convert high-density lipoproteins into pro-atherogenic particles

et al. 2021

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High-density lipoproteins (HDLs) are a group of different subpopulations of sialylated particles that have an essential role in the reverse cholesterol transport (RCT) pathway. Importantly, changes in the protein and lipid composition of HDLs may lead to the formation of particles with reduced atheroprotective properties. Here, we show that Streptococcus pneumoniae pneumolysin (PLY) and neuraminidase A (NanA) impair HDL function by causing chemical and structural modifications of HDLs. The proteomic, lipidomic, cellular, and biochemical analysis revealed that PLY and NanA induce significant changes in sialic acid, protein, and lipid compositions of HDL. The modified HDL particles have reduced cholesterol acceptor potential from activated macrophages, elevated levels of malondialdehyde adducts, and show significantly increased complement activating capacity. These results suggest that accumulation of these modified HDL particles in the arterial intima may present a trigger for complement activation, inflammatory response, and thereby promote atherogenic disease progression.

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Glycosylation of human plasma lipoproteins reveals a high level of diversity, which directly impacts their functional properties

Abstract: Glycosylation of human plasma lipoproteins reveals a high level of diversity, which directly impacts their functional properties

Cited by 26 publications

References 67 publications

A puzzle piece of protein N-glycosylation in chicken egg: N-glycoproteome of chicken egg vitelline membrane

A puzzle piece of protein N-glycosylation in chicken egg: N-glycoproteome of chicken egg vitelline membrane

Plasma N-Glycans as Emerging Biomarkers of Cardiometabolic Risk: A Prospective Investigation in the EPIC-Potsdam Cohort Study

Streptococcus pneumoniae pneumolysin and neuraminidase A convert high-density lipoproteins into pro-atherogenic particles

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