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Effect of Experimental Thyrotoxicosis onto Blood Coagulation: A Proteomics Study
- Background: Hyperthyroidism is known to induce a hypercoagulable state. It stimulates plasma levels of procoagulative factors and reduces fibrinolytic activity. So far most of the data have been derived from patients with endogenous hyperthyroidism with a wide variability in the underlying pathogenesis and severity of the disease. Objectives: In this study we experimentally induced thyrotoxicosis in healthy volunteers to explore the effects of thyroxine excess on the plasma proteome. Using a shotgun proteomics approach, the abundance of plasma proteins was monitored before, during and after thyrotoxicosis. Methods: Sixteen healthy male subjects were sampled at baseline, 4 and 8 weeks under 250 µg/day thyroxine p.o., as well as 4 and 8 weeks after stopping the application. Plasma proteins were analyzed after depletion of 6 high-abundance proteins (MARS6) by LC-ESI-MS/MS mass spectrometry. Mass spectrometric raw data were processed using a label-free, intensity-based workflow. Subsequently, the linear dependence between protein abundances and fT<sub>4</sub> levels were calculated using a Pearson correlation. Results: All subjects developed biochemical thyrotoxicosis, and this effect was reversed within the first 4 weeks of follow-up. None of the volunteers noticed any subjective symptoms. Levels of 10 proteins involved in the coagulation cascade specifically correlated with fT<sub>4</sub>, supporting an influence of thyroid hormone levels on blood coagulation even at nonpathological levels. Conclusions: The results suggest that experimental thyrotoxicosis exerts selective and specific thyroxine-induced effects on coagulation markers. Our study design allows assessment of thyroid hormone effects on plasma protein levels without secondary effects of other diseases or therapies.
Author: | Beatrice Engelmann, Julia Bischof, Anne-Luise Dirk, Nele Friedrich, Elke Hammer, Thomas Thiele, Dagmar Führer, Georg Homuth, Georg Brabant, Uwe Völker |
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URN: | urn:nbn:de:gbv:9-opus-31257 |
URL: | http://www.karger.com/etj |
DOI: | https://doi.org/10.1159/000381769 |
ISSN: | 2235-0640 |
ISSN: | 2235-0802 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/26601083 |
Parent Title (English): | European Thyroid Journal |
Publisher: | S. Karger AG |
Place of publication: | Basel, Switzerland |
Document Type: | Article |
Language: | English |
Date of first Publication: | 2015/05/28 |
Release Date: | 2020/09/29 |
Tag: | Coagulation; Free thyroxine; Label-free quantification; Plasma; Shotgun proteomics |
GND Keyword: | - |
Volume: | 4 |
Issue: | Suppl 1 |
First Page: | 119 |
Last Page: | 124 |
Faculties: | Universitätsmedizin / Institut für Immunologie u. Transfusionsmedizin - Abteilung Transfusionsmedizin |
Licence (German): | Urheberrechtlich geschützt |