Glucocorticoid effects on angiogenesis are associated with mTOR pathway activity

Area of Science:

• Reproductive biology
• Cellular and molecular biology
• Pharmacology

Background:

• Glucocorticoids (GC) are frequently used during pregnancy.
• Their precise effects on pro-angiogenic factors and receptors remain unclear.
• Understanding these effects is crucial for maternal and fetal health.

Purpose of the Study:

• To investigate the impact of synthetic GC (triamcinolone acetonide) on key angiogenic factors (VEGF, PIGF) and their receptors (VEGFR1, VEGFR2).
• To explore the association between GC exposure and the Akt/mTOR signaling pathway.
• To assess the functional consequences on endothelial cell vascular network formation.

Main Methods:

• Incubation of human umbilical vein endothelial cells (HUVECs) with triamcinolone acetonide (TA).
• Measurement of protein and mRNA expression levels of VEGF, PIGF, VEGFR1, and VEGFR2.
• Analysis of Akt/mTOR pathway components (phospho-mTOR, phospho-Akt, phospho-p70S6K, phospho-4EBP1).
• Assessment of HUVEC vascular network forming capacity.

Main Results:

• TA decreased cellular and soluble VEGF and VEGFR1 protein expression.
• TA increased soluble VEGFR2 expression.
• VEGF, VEGFR1, and VEGFR2 mRNA levels were altered in a time- and dose-dependent manner.
• PIGF protein was unaffected, but PIGF mRNA decreased dose-dependently.
• While Akt/mTOR phosphorylation was unchanged, downstream targets (phospho-p70S6K, phospho-4EBP1) and vascular network formation capacity decreased dose-dependently.
• GC exposure negatively affects angiogenesis via the Akt/mTOR pathway.

Conclusions:

• Glucocorticoids exert detrimental effects on angiogenesis.
• These effects are mediated by alterations in angiogenic factor and receptor expression and vascular network formation capacity.
• The Akt/mTOR pathway plays a role in mediating these adverse effects.