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Transforming Growth Factor β1 (TGFβ1) and Vascular Endothelial Growth Factor (VEGF) in the blood of healthy people and patients with Graves’ orbitopathy — a new mechanism of glucocorticoids action?
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Abstract
Introduction: The first part of this paper is related to healthy people and presents concentrations of TGFβ1 and VEGF in blood (with and without dividing data with respect to sex), their single measurement values (at 8 am), Mean Daily Concentrations (MDC), Area Under the Curves (AUC; total daily secretion), and circadian rhythm. The second part of the work is related to Graves’ orbitopathy (GO). The aim of the study were: 1) to determine the physiological pattern of TGFβ1 and VEGF secretion; 2) to compare the serum TGFβ1 and VEGF circadian profile in newly diagnosed thyreotoxic patients with active GO and healthy controls (H); and 3) to estimate the influence of high-dose intravenous methylprednisolone pulse therapy (MP) on TGFb1 and VEGF blood levels in GO.
Material and methods: Twenty-two healthy (H) subjects and 16 hyperthyroid GO patients were treated with MP (6 g/14 days) and followed up by ophthalmological assessment. Blood was collected before and after 2 weeks MP-therapy. TGFβ1 and VEGF levels were determined by the ELISA method.
Results: No difference was observed in the concentrations of TGFβ1 and VEGF in the blood of healthy women and men — in further analysis, a combined healthy male and female cohort was used (H). While the absence of circadian rhythms in the concentrations of TGFβ1 and VEGF allows the application of a single measurement approach, MDC and AUC measurements were found to be more precise. There were no differences in TGFβ1 MDC/AUC between GO and H. VEGF MDC/AUC in GO were higher than in H. MP-therapy increased TGFb1 MDC/AUC, thus in GO after MP, the TGFβ1 MDC/AUC were higher than in H. There were no differences in VEGF MDC/AUC during MP-therapy. MP-therapy was effective in 15/16 patients.
Conclusions:
1. MP-therapy increases MDC and AUC of TGFβ1. The effectiveness of MP-therapy in patients with active GO may be related to its influence on TGFβ1 concentrations in blood. The results suggest the existence of a new mechanism of glucocorticoids action, consisting of an increase in the secretion of TGFβ1.
2. The elevated serum VEGF in thyreotoxic patients with active GO may reflect long-standing autoimmune processes in orbital and thyroid tissues and intensified angiogenesis in the thyroid gland. (Endokrynol Pol 2014; 65 (5): 348–356)
Abstract
Introduction: The first part of this paper is related to healthy people and presents concentrations of TGFβ1 and VEGF in blood (with and without dividing data with respect to sex), their single measurement values (at 8 am), Mean Daily Concentrations (MDC), Area Under the Curves (AUC; total daily secretion), and circadian rhythm. The second part of the work is related to Graves’ orbitopathy (GO). The aim of the study were: 1) to determine the physiological pattern of TGFβ1 and VEGF secretion; 2) to compare the serum TGFβ1 and VEGF circadian profile in newly diagnosed thyreotoxic patients with active GO and healthy controls (H); and 3) to estimate the influence of high-dose intravenous methylprednisolone pulse therapy (MP) on TGFb1 and VEGF blood levels in GO.
Material and methods: Twenty-two healthy (H) subjects and 16 hyperthyroid GO patients were treated with MP (6 g/14 days) and followed up by ophthalmological assessment. Blood was collected before and after 2 weeks MP-therapy. TGFβ1 and VEGF levels were determined by the ELISA method.
Results: No difference was observed in the concentrations of TGFβ1 and VEGF in the blood of healthy women and men — in further analysis, a combined healthy male and female cohort was used (H). While the absence of circadian rhythms in the concentrations of TGFβ1 and VEGF allows the application of a single measurement approach, MDC and AUC measurements were found to be more precise. There were no differences in TGFβ1 MDC/AUC between GO and H. VEGF MDC/AUC in GO were higher than in H. MP-therapy increased TGFb1 MDC/AUC, thus in GO after MP, the TGFβ1 MDC/AUC were higher than in H. There were no differences in VEGF MDC/AUC during MP-therapy. MP-therapy was effective in 15/16 patients.
Conclusions:
1. MP-therapy increases MDC and AUC of TGFβ1. The effectiveness of MP-therapy in patients with active GO may be related to its influence on TGFβ1 concentrations in blood. The results suggest the existence of a new mechanism of glucocorticoids action, consisting of an increase in the secretion of TGFβ1.
2. The elevated serum VEGF in thyreotoxic patients with active GO may reflect long-standing autoimmune processes in orbital and thyroid tissues and intensified angiogenesis in the thyroid gland. (Endokrynol Pol 2014; 65 (5): 348–356)
Keywords
TGFbeta1; VEGF; transforming growth factor beta 1; vascular-endothelial growth factor; healthy; thyroid; Graves; orbitopathy; fibrosis; angiogenesis; methylprednisolone; glucocorticoids
About this articleTitle
Transforming Growth Factor β1 (TGFβ1) and Vascular Endothelial Growth Factor (VEGF) in the blood of healthy people and patients with Graves’ orbitopathy — a new mechanism of glucocorticoids action?
Journal
Issue
Article type
Original paper
Pages
348-356
Published online
2014-10-09
Page views
2495
Article views/downloads
2557
DOI
10.5603/EP.2014.0048
Bibliographic record
Endokrynol Pol 2014;65(5):348-356.
Keywords
TGFbeta1
VEGF
transforming growth factor beta 1
vascular-endothelial growth factor
healthy
thyroid
Graves
orbitopathy
fibrosis
angiogenesis
methylprednisolone
glucocorticoids
Authors
Dariusz Kajdaniuk
Bogdan Marek
Danuta Niedziołka-Zielonka
Wanda Foltyn
Mariusz Nowak
Lucyna Siemińska
Halina Borgiel-Marek
Joanna Głogowska-Szeląg
Zofia Ostrowska
Lucjan Drożdż
Beata Kos-Kudła
