The role of fibrinogen glycation in ATTR: evidence for chaperone activity loss in disease

Fonseca, Daniel; Gilberto, Samuel; Ribeiro-Silva, Cristina; Ribeiro, Raquel; Guinote, Inês Batista; Saraiva, Susana; Gomes, Ricardo A.; Mateus, Élia; Viana, Ana S.; Barroso, Eduardo; Freire, Ana Ponces; Freire, Patrick; Cordeiro, Carlos; Costa, Gustavo

doi:10.1042/bcj20160290

Cited by 4 publications

(2 citation statements)

References 67 publications

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“…Of the chaperones identified in this study, fibrinogen is the only chaperone that has previously been reported to directly interact with TTR (da Costa et al, 2011;Tang et al, 2009b). The chaperone activity of FGA is based on the isoform fibrinogen-420 (Tang et al, 2009a), and glycation of FGA results in a loss of function (Fonseca et al, 2016). Moreover, FGA can cause amyloid deposition as a consequence of genetic mutation (Yazaki et al, 2018).…”

Section: Discussionmentioning

confidence: 75%

Hepatocyte-like cells reveal novel role of SERPINA1 in transthyretin amyloidosis

Niemietz

Fleischhauer

Sandfort

et al. 2018

Journal of Cell Science

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Transthyretin (TTR)-related familial amyloid polyneuropathy (ATTR) results from aggregation and extracellular disposition of misfolded TTR mutants. Growing evidence suggests the importance of hepatic chaperones for the modulation of pathogenesis. We took advantage of induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells (HLCs) from ATTR patients (ATTR-HLCs) to compare chaperone gene expression to that in HLCs from healthy individuals (H-HLCs). From the set of genes analyzed, chaperones that are predominantly located extracellularly were differently expressed. Expression of the chaperones showed a high correlation with TTR in both ATTR-HLCs and H-HLCs. In contrast, after TTR knockdown, the correlation was mainly affected in ATTR-HLCs suggesting that differences in TTR expression triggers aberrant chaperone expression. Serpin family A member 1 (SERPINA1) was the only extracellular chaperone that was markedly upregulated after TTR knockdown in ATTR-HLCs. Co-immunoprecipitation revealed that SERPINA1 physically interacts with TTR. In vitro assays indicated that SERPINA1 can interfere with TTR aggregation. Taken together, our results suggest that extracellular chaperones play a crucial role in ATTR pathogenesis, in particular SERPINA1, which may affect amyloid formation.

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Section: Discussionmentioning

confidence: 75%

Hepatocyte-like cells reveal novel role of SERPINA1 in transthyretin amyloidosis

Niemietz

Fleischhauer

Sandfort

et al. 2018

Journal of Cell Science

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“…Factors such as hyperfibrinogenemia, hyperinsulinemia, dyslipidemia, hypertension, obesity, decreased fibrinolysis, endothelial dysfunction, and changed platelet aggregability are known to influence thrombus formation in these individuals. 11,14–16,19–24 For example, fibrinogen concentration is an established independent risk factor for cardiovascular disease, regardless of vascular event history. 25–29 Additionally, in animal studies, it is known that hyperfibrinogenemic mice exhibit changed fibrin fiber characteristics, quicker vessel occlusion, increased fibrin mass, and poor fibrinolytic behavior when compared to nonhyperfibrinogenemic controls.…”

Section: Introductionmentioning

confidence: 99%

Glucose Concentration Affects Fibrin Clot Structure and Morphology as Evidenced by Fluorescence Imaging and Molecular Simulations

Hood

Yesudasan

Averett

2018

Clin Appl Thromb Hemost

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Although in vivo studies have been conducted in the past to determine hyperglycemic effects and influence on clotting risk in patients with diabetes, the true extent of hyperglycemia on unstable and spontaneous clot formation remains highly debated. Factors such as increased glycation, elevated fibrinogen concentration, elevated prothrombin levels, and decreased plasminogen are known to influence fibrin conversion, clot morphology, and thrombus formation in these individuals. In this regard, the isolated effects of hyperglycemia on irregular fibrin clot formation were investigated in a controlled fibrinogen system. In this study, fibrin clot characteristic differences at 3 glucose concentrations were analyzed to determine the effects of glucose concentration on fibrinogen glycation and fibrin clot morphology using confocal microscopy, glycation quantification, molecular simulations, and image processing methods. Algorithms coupled with statistical analysis support in vivo findings that hyperglycemia increases fibrinogen glycation, with ensuing altered fibrin clot structure characteristics. Our experimental and molecular simulation results consistently show an increased glucose adsorption by fibrinogen with increased glucose concentration. Significant differences in clot structure characteristics were observed, and the results of this work can be used to further develop diagnostic tools for evaluating clotting risk in individuals with hypercoagulable and hyperglycemic conditions.

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Analysis of Carbohydrates and Glycoconjugates by Matrix‐assisted Laser Desorption/Ionization Mass Spectrometry: An Update for 2015–2016

Harvey

2021

Mass Spectrometry Reviews

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This review is the ninth update of the original article published in 1999 on the application of matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings coverage of the literature to the end of 2016. Also included are papers that describe methods appropriate to analysis by MALDI, such as sample preparation techniques, even though the ionization method is not MALDI. Topics covered in the first part of the review include general aspects such as theory of the MALDI process, matrices, derivatization, MALDI imaging, fragmentation and arrays. The second part of the review is devoted to applications to various structural types such as oligo‐ and poly‐saccharides, glycoproteins, glycolipids, glycosides and biopharmaceuticals. Much of this material is presented in tabular form. The third part of the review covers medical and industrial applications of the technique, studies of enzyme reactions and applications to chemical synthesis. The reported work shows increasing use of combined new techniques such as ion mobility and the enormous impact that MALDI imaging is having. MALDI, although invented over 30 years ago is still an ideal technique for carbohydrate analysis and advancements in the technique and range of applications show no sign of deminishing. © 2020 Wiley Periodicals, Inc.

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The role of fibrinogen glycation in ATTR: evidence for chaperone activity loss in disease

Cited by 4 publications

References 67 publications

Hepatocyte-like cells reveal novel role of SERPINA1 in transthyretin amyloidosis

Hepatocyte-like cells reveal novel role of SERPINA1 in transthyretin amyloidosis

Glucose Concentration Affects Fibrin Clot Structure and Morphology as Evidenced by Fluorescence Imaging and Molecular Simulations

Analysis of Carbohydrates and Glycoconjugates by Matrix‐assisted Laser Desorption/Ionization Mass Spectrometry: An Update for 2015–2016

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