title: Glucocorticoid effects on angiogenesis are associated with mTOR pathway activity.
abstract: Glucocorticoids (GC) often are administered during pregnancy, but despite their widespread use in clinical practice, it remains uncertain how GC exposure affects pro-angiogenic factors and their receptors. We investigated the effects of GC on vascular endothelial growth factor (VEGF), placental growth factor (PIGF), vascular endothelial growth factor receptor 1 (VEGFR1) and vascular endothelial growth factor receptor 2 (VEGFR2) protein and mRNA expressions and investigated the possible association of GC with the Akt/mTOR pathway. We incubated human umbilical vein endothelial cells (HUVECs) with a synthetic GC, triamcinolone acetonide (TA). TA administration caused decreased cellular and soluble VEGF and VEGFR1 protein expressions and increased soluble VEGFR2 expression. VEGF, VEGFR1 and VEGFR2 mRNA expressions were altered in a time and dose dependent manner. PIGF protein expression was unaffected by TA treatment, but PIGF mRNA expression decreased in a dose dependent manner after incubation for 48 and 72 h. Phospho-mTOR and phospho-Akt expressions were unaffected. Phospho-p70S6K and phospho-4EBP1 protein expressions and the vascular network forming capacity of HUVECs decreased in a dose dependent manner. We found that GC exert detrimental effects on angiogenesis by altering cellular and soluble angiogenic protein and mRNA levels, and vascular network forming capacities by the Akt/mTOR pathway.
authors.affiliation: a Department of Histology , Embryology, Akdeniz University , Antalya , Turkey.
authors.forename: A
authors.initials: A
authors.lastname: Ozmen
authors.affiliation: a Department of Histology , Embryology, Akdeniz University , Antalya , Turkey.
authors.forename: G
authors.initials: G
authors.lastname: Unek
authors.affiliation: b Department of Biochemistry , Akdeniz University , Antalya , Turkey.
authors.forename: D
authors.initials: D
authors.lastname: Kipmen-Korgun
authors.affiliation: c Department of Obstetrics , Gynecology, Medical Faculty, Akdeniz University , Antalya , Turkey.
authors.forename: I
authors.initials: I
authors.lastname: Mendilcioglu
authors.affiliation: c Department of Obstetrics , Gynecology, Medical Faculty, Akdeniz University , Antalya , Turkey.
authors.forename: C
authors.initials: C
authors.lastname: Sanhal
authors.affiliation: c Department of Obstetrics , Gynecology, Medical Faculty, Akdeniz University , Antalya , Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Sakıncı
authors.affiliation: a Department of Histology , Embryology, Akdeniz University , Antalya , Turkey.
authors.forename: E T
authors.initials: ET
authors.lastname: Korgun
mesh_terms: D043924:Angiogenesis Modulating Agents / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011247:Pregnancy; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D043924:Angiogenesis Modulating Agents; D005938:Glucocorticoids; D042461:Vascular Endothelial Growth Factor A; C546842:MTOR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; D058570:TOR Serine-Threonine Kinases
keywords: Akt/mTOR; angiogenesis; glucocorticoid; human umbilical vein endothelial cells; placental growth factor; steroids; triamcinolone acetonide; vascular endothelial growth factor