Combined High-Density Lipoprotein Proteomic and Glycomic Profiles in Patients at Risk for Coronary Artery Disease

Krishnan, Sridevi; Huang, Jincui; Lee, Hyeyoung; Guerrero, Andrés; Berglund, Lars; Anuurad, Erdembileg; Lebrilla, Carlito B.; Zivkovic, Angela M.

doi:10.1021/acs.jproteome.5b00730

Cited by 36 publications

(36 citation statements)

References 64 publications

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“…Glycosylation is of high interest for the development or improvement of biomarkers for disease and patient stratification (14,97). In particular, the findings within this study may be of benefit to the detection and discrimination of metabolic syndrome or inflammatory disorders, and may bolster the predictability of existing biomarkers such as the Framingham Risk Score (98).…”

Section: Discussionmentioning

confidence: 90%

Human Plasma N-glycosylation as Analyzed by Matrix-Assisted Laser Desorption/Ionization-Fourier Transform Ion Cyclotron Resonance-MS Associates with Markers of Inflammation and Metabolic Health

Reiding

Ruhaak

et al. 2017

Molecular & Cellular Proteomics

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Glycosylation is an abundant co-and post-translational protein modification of importance to protein processing and activity. Although not template-defined, glycosylation does reflect the biological state of an organism and is a high-potential biomarker for disease and patient stratification. However, to interpret a complex but informative sample like the total plasma N-glycome, it is important to establish its baseline association with plasma protein levels and systemic processes. Thus far, large-scale studies (n >200) of the total plasma N-glycome have been performed with methods of chromatographic and electrophoretic separation, which, although being informative, are limited in resolving the structural complexity of plasma N-glycans. MS has the opportunity to contribute additional information on, among others, antennarity, sialylation, and the identity of high-mannose type species.Here, we have used matrix-assisted laser desorption/ ionization ( Glycosylation is a ubiquitous co-and post-translational protein modification of functional relevance to the processing and activity of the conjugate. Examples include quality control during protein folding, regulation of circulatory half-life, and modulation of receptor interactions by either providing the recognition motif or by affecting protein conformation (1-7). Consequentially, glycosylation has been associated with a multitude of diseases and states thereof, among which the progression and metastasis of cancer and the remission of rheumatoid arthritis (8 -11). Because the process of glycosylation is not template-defined, glycosylation integrates a large series of cellular conditions such as glycosidase/glycosyltransferase abundance and activity, endoplasmic reticulum From the ‡Center

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Section: Discussionmentioning

confidence: 90%

Human Plasma N-glycosylation as Analyzed by Matrix-Assisted Laser Desorption/Ionization-Fourier Transform Ion Cyclotron Resonance-MS Associates with Markers of Inflammation and Metabolic Health

Reiding

Ruhaak

et al. 2017

Molecular & Cellular Proteomics

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“…These data showing the procoagulant activity of SAA4 provides biological plausibility for a potential causal prothrombotic role for SAA4. SAA4 may act as a template for the formation of the prothrombinase complex in certain pathologies where SAA4 is deposited, as in the atheroma plaque where significant amounts of SAA4 are found . These findings also raise the possibility that SAA4 procoagulant activity might contribute to normal hemostasis.…”

Section: Resultsmentioning

confidence: 99%

“…Constitutive SAA4, where “constitutive” denotes its level is not subject to remarkable alterations, is linked to a certain group of HDL particles (HDL 3 ) . More recent studies have identified a minor portion of SAA4 that is in the LDL and VLDL subfractions . SAA4 comprises >90% of the total serum SAA proteins in the absence of inflammatory pathologies with a serum concentration of 42 to 86 µg/mL, which is high in comparison with basal acute‐phase SAA (SAA1 plus SAA2) levels (average, 1‐2 µg/mL) .…”

Section: Introductionmentioning

confidence: 99%

“…17 More recent studies have identified a minor portion of SAA4 that is in the LDL and VLDL subfractions. 18,19 SAA4 comprises >90% of the total serum SAA proteins 17 in the absence of inflammatory pathologies with a serum concentration of 42 to 86 µg/mL, which is high in comparison with basal acute-phase SAA (SAA1 plus SAA2) levels (average, 1-2 µg/ mL). 9,12,13 SAA4 expression is implicated during inflammation including atherosclerosis; notably, SAA4 lacks expression in normal arteries but is expressed in carotid lesions.…”

Section: Introductionmentioning

confidence: 99%

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Serum amyloid A4 is a procoagulant apolipoprotein that it is elevated in venous thrombosis patients

Fernández

Deguchi

Elias

et al. 2020

Research and Practice in Thrombosis and Haemostasis

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Background Serum amyloid A4 (SAA4) is an apolipoprotein that is in the SAA family and it is constitutively translated. Previously, acute‐phase SAA1 and SAA2 levels were associated with venous thromboembolism (VTE). Objective We investigated the association of plasma SAA4 with VTE and the role of SAA4 in coagulation. Patients and Methods The association of SAA4 with VTE in a case‐control study of adult VTE subjects (N = 113 each group) and the effects of recombinant SAA4 on plasma blood coagulation assays and prothrombin activation initiated by factor Xa were evaluated. Results Plasma SAA4 levels in VTE subjects were higher vs. controls (48.1 vs. 38.4 µg/mL; P < .001). Elevated plasma SAA4 level (above the 90th percentile of controls) was associated with increased VTE occurrence (odds ratio, 3.8; 95% confidence interval, 1.8‐8.0). This association remained significant after the adjustment for acute‐phase SAA level, suggesting that SAA4 associated with VTE is independent of acute‐phase SAA. Two isoforms of SAA4, that is, glycosylated and nonglycosylated SAA4 isoforms, were each higher in VTE patients. When recombinant SAA4 was added to plasma, it shortened factor Xa‐1‐stage clotting times, showing that it enhances clotting in plasma. In reaction mixtures containing purified factors Xa and Va and prothrombin, recombinant SAA4 increased prothrombin activation, showing that it enhances prothrombinase activity. Conclusion Elevated plasma constitutive SAA4 levels were linked to VTE in adults, and SAA4 can enhance thrombin generation in plasma. Our data highlight a previously unknown procoagulant activity of SAA4 that appears to be related to risk of venous thrombotic events.

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“…Each specific sialyltransferase is expressed to synthesize ganglioside and regulated to meet certain cellular demands such as growth, signaling, apoptosis, infection, oncogenesis, and atherosclerotic diseases. In atherosclerotic disease, the levels of specific gangliosides are increased in plasma [Krishnan et al, ] and gangliosides are accumulated in atherosclerotic vessels and intimal atherosclerotic plaques [Prokazova et al, ; Moon et al, ]. Thus, we have previously hypothesized that cellular gangliosides biosynthesis regulates the level of plasma lipoprotein metabolism and secretion [Kang et al, ].…”

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confidence: 99%

Monosialyl Ganglioside GM3 Decreases Apolipoprotein B-100 Secretion in Liver Cells

et al. 2017

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Some sialic acid-containing glycolipids are known to regulate development of atherosclerosis with accumulated plasma apolipoprotein B-100 (Apo-B)-containing lipoproteins, because Apo-B as an atherogenic apolipoprotein is assembled mainly in VLDL and LDL. Previously, we have elucidated that disialyl GD3 promotes the microsomal triglyceride transfer protein (MTP) gene expression and secretion of triglyceride (TG)-assembled ApoB, claiming the GD3 role in ApoB lipoprotein secretion in liver cells. In the synthetic pathway of gangliosides, GD3 is synthesized by addition of a sialic acid residue to GM3. Thus, there should be some regulatory links between GM3 and GD3. In this study, exogenous and endogenous monosialyl GM3 has been examined how GM3 plays a role in ApoB secretion in Chang liver cells in a view point of MTP and ApoB degradation in the same cells. The level of GM3 ganglioside in the GM3 synthase gene-transfected cells was increased in the cell extract, but not in the medium. In addition, GM3 synthase gene-transfected cells showed a diminished secretion of TG-enriched ApoB with a lower content of TG in the medium. Exogenous GM3 treatment for 24 h exerted a dose dependent inhibitory effect on ApoB secretion together with TG, while a liver-specific albumin was unchanged, indicating that GM3 effect is limited to ApoB secretion. GM3 decreased the mRNA level of MTP gene, too. ApoB protein assembly dysregulated by GM3 indicates the impaired ApoB secretion is caused by a proteasome-dependent pathway. Treatment with small interfering RNAs (siRNAs) decreased ApoB secretion, but GM3-specific antibody did not. These results indicate that plasma membrane associated GM3 inhibits ApoB secretion, lowers development of atherosclerosis by decreasing the secretion of TG-enriched ApoB containing lipoproteins, suggesting that GM3 is an inhibitor of ApoB and TG secretion in liver cells. J. Cell. Biochem. 118: 2168-2181, 2017. © 2017 Wiley Periodicals, Inc.

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Combined High-Density Lipoprotein Proteomic and Glycomic Profiles in Patients at Risk for Coronary Artery Disease

Cited by 36 publications

References 64 publications

Human Plasma N-glycosylation as Analyzed by Matrix-Assisted Laser Desorption/Ionization-Fourier Transform Ion Cyclotron Resonance-MS Associates with Markers of Inflammation and Metabolic Health

Human Plasma N-glycosylation as Analyzed by Matrix-Assisted Laser Desorption/Ionization-Fourier Transform Ion Cyclotron Resonance-MS Associates with Markers of Inflammation and Metabolic Health

Serum amyloid A4 is a procoagulant apolipoprotein that it is elevated in venous thrombosis patients

Monosialyl Ganglioside GM3 Decreases Apolipoprotein B-100 Secretion in Liver Cells

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