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Generation of a Mouse Spontaneous Autoimmune Thyroiditis Model
Published on: March 17, 2023
Advanced glycation end products (AGEs) and its receptors in the pathogenesis of hyperthyroidism
Gudrun Caspar-Bell1, Indu Dhar2, Kailash Prasad3
1Department of Medicine and Royal University Hospital, University of Saskatchewan, Saskatoon, SK, Canada.
Abstract:
Oxidative stress has been implicated in the pathogenesis of hyperthyroidism and its complications. Interaction of advanced glycation end products (AGEs) with receptor RAGE (receptor for AGEs) generates reactive oxygen species. Soluble receptor for AGEs (sRAGE) competes with RAGE for binding with AGEs and attenuates the generation of ROS. Low levels sRAGE and high levels AGEs would generate more ROS leading to hyperthyroidism and its complications. The objectives are to determine if levels of serum sRAGE are low and the levels of AGEs and AGEs/sRAGE are high in patients with hyperthyroidism. The study subjects comprised of 33 patients with hyperthyroidism and 20 controls. Levels of serum sRAGE were lower, while that of AGEs and AGEs/sRAGE were higher in patients compared to controls, being significant only for sRAGE and AGEs/sRAGE. When the levels of sRAGE, AGEs, and AGEs/sRAGE were assessed for hyperthyroidism associated with different diseases, the levels of sRAGE were lower in Hashimoto disease, and levels of AGEs were higher in patients with Graves' disease compared to control. The levels of AGEs/sRAGE were elevated in an all except patients with Hashimoto disease. The levels of AGEs, sRAGE, or AGEs/RAGE were not correlated with age, weight, and blood pressures except systolic pressure which was inversely correlated with sRAGE. The levels of sRAGE were negatively correlated with AGEs and AGEs/sRAGE. The levels of AGEs/sRAGE were positively correlated with AGEs. In conclusion, low levels of sRAGE, and high levels of AGEs and AGEs/sRAGE are risk biomarkers in the pathogenesis hyperthyroidism and its complications.
Insights
Low levels of soluble receptor for advanced glycation end products (sRAGE) and high levels of advanced glycation end products (AGEs) and their ratio (AGEs/sRAGE) are linked to hyperthyroidism. These biomarkers may indicate increased oxidative stress and disease complications.
Area of Science:
- Endocrinology
- Oxidative Stress Research
- Biomarker Discovery
Background:
- Oxidative stress contributes to hyperthyroidism pathogenesis and complications.
- Advanced glycation end products (AGEs) binding to receptor RAGE generates reactive oxygen species (ROS).
- Soluble RAGE (sRAGE) counteracts RAGE-AGEs interaction, reducing ROS.
Purpose of the Study:
- To investigate serum sRAGE, AGEs, and AGEs/sRAGE levels in hyperthyroidism patients.
- To assess these biomarkers in relation to hyperthyroidism and associated conditions.
- To explore correlations between biomarkers and clinical parameters.
Main Methods:
- Serum samples from 33 hyperthyroidism patients and 20 controls were analyzed.
- Levels of sRAGE and AGEs were quantified.
- AGEs/sRAGE ratio was calculated and compared between groups.
Main Results:
- Hyperthyroidism patients showed significantly lower sRAGE and higher AGEs/sRAGE compared to controls.
- sRAGE levels were lower in Hashimoto disease; AGEs levels were higher in Graves' disease.
- AGEs/sRAGE was elevated in all subgroups except Hashimoto disease.
- sRAGE negatively correlated with AGEs and AGEs/sRAGE.
Conclusions:
- Low sRAGE and high AGEs/sRAGE are potential risk biomarkers for hyperthyroidism.
- These biomarkers may play a role in the pathogenesis and complications of hyperthyroidism.
- AGEs/sRAGE ratio appears particularly relevant across different hyperthyroid conditions.
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