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Open AccessArticle

Plasma-Based Proteomics Profiling of Patients with Hyperthyroidism after Antithyroid Treatment

1
Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, P.O. Box 2925 (98), Riyadh 11461, Saudi Arabia
2
Department of Medicine, College of Medicine and king Saud Medical City, King Saud University, P.O. Box 2925 (98), Riyadh 11461, Saudi Arabia
*
Author to whom correspondence should be addressed.
Academic Editors: Pierluigi Luigi Mauri, Martina Marchetti-Deschmann and Diana Canetti
Molecules 2020, 25(12), 2831; https://doi.org/10.3390/molecules25122831
Received: 3 May 2020 / Revised: 14 June 2020 / Accepted: 17 June 2020 / Published: 19 June 2020
(This article belongs to the Special Issue Mass Spectrometric Proteomics II)
Thyroid hormones critically modulate body homeostasis and haemostasis by regulating energy and metabolism. Previous studies have focused on individual pathways or proteins that are affected by increases in thyroid hormone levels, while an overall plasma proteomic signature of this increased level is lacking. Herein, an integrated untargeted proteomic approach with network analysis was used to identify changes in circulating proteins in the plasma proteome between hyperthyroid and euthyroid states. Plasma from 10 age-matched subjects at baseline (hyperthyroid) and post treatment with carbimazole (euthyroid) was compared by difference gel electrophoresis (DIGE) and matrix-assisted laser desorption/ionization time of flight (MALDI TOF) mass spectrometry (MS). A total of 20 proteins were identified with significant difference in abundance (analysis of variance (ANOVA) test, p ≤ 0.05; fold-change ≥ 1.5) between the two states (12 increased and 8 decreased in abundance in the hyperthyroid state). Twelve protein spots corresponding to ten unique proteins were significantly more abundant in the hyperthyroid state compared with the euthyroid state. These increased proteins were haptoglobin (HP), hemopexin (HPX), clusterin (CLU), apolipoprotein L1 (APOL1), alpha-1-B glycoprotein (A1BG), fibrinogen gamma chain (FGG), Ig alpha-1 chain C region (IGHA1), complement C6 (C6), leucine rich alpha 2 glycoprotein (LRG1), and carboxypeptidase N catalytic chain (CPN1). Eight protein spots corresponding to six unique proteins were significantly decreased in abundance in the hyperthyroid samples compared with euthyroid samples. These decreased proteins were apolipoprotein A1 (APOA1), inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4), plasminogen (PLG), alpha-1 antitrypsin (SERPINA1), fibrinogen beta chain (FGB), and complement C1r subcomponent (C1R). The differentially abundant proteins were investigated by ingenuity pathway analysis (IPA). The network pathway identified related to infectious disease, inflammatory disease, organismal injury and abnormalities, and the connectivity map focused around two central nodes, namely the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and p38 mitogen-activated protein kinase (MAPK) pathways. The plasma proteome of patients with hyperthyroidism revealed differences in the abundance of proteins involved in acute phase response signaling, and development of a hypercoagulable and hypofibrinolytic state. Our findings enhance our existing knowledge of the altered proteins and associated biochemical pathways in hyperthyroidism. View Full-Text
Keywords: hyperthyroidism; plasma proteomics; inflammation; acute phase proteins; apolipoproteins; hypercoagulability; carbimazole; ingenuity pathway analysis hyperthyroidism; plasma proteomics; inflammation; acute phase proteins; apolipoproteins; hypercoagulability; carbimazole; ingenuity pathway analysis
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Masood, A.; Benabdelkamel, H.; Ekhzaimy, A.A.; Alfadda, A.A. Plasma-Based Proteomics Profiling of Patients with Hyperthyroidism after Antithyroid Treatment. Molecules 2020, 25, 2831.

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