K W Yi1, S H Jung2, G J Cho1, H J Seol3, S C Hong1, M J Oh4, H J Kim1. 1. Department of Obstetrics and Gynecology, College of Medicine, Korea University, Seoul, South Korea. 2. Department of Obstetrics and Gynecology, Bundang CHA University hospital, Gyeonggi, South Korea. Electronic address: aa2346@chamc.co.kr. 3. Department of Obstetrics and Gynecology, Kyung Hee University hospital, Seoul, South Korea. 4. Department of Obstetrics and Gynecology, College of Medicine, Korea University, Seoul, South Korea. Electronic address: mjohmd@korea.ac.kr.
Abstract
INTRODUCTION: Soluble fms-like tyrosine kinase-1 (sFlt-1) is a vascular endothelial growth factor (VEGF) binding protein and potent antagonist of VEGF. Alpha 2 macroglobulin (α2M) is another major binding protein for circulating VEGF, which is present in human plasma at higher concentration (2-4 mg/mL) than sFlt-1. This study investigated the effects of sFlt-1 and α2M on VEGF-induced endothelin-1 (ET-1) upregulation in human microvascular endothelial cell-1 (HMEC-1). METHODS: HMEC-1 was cultured and incubated with varying concentrations of sFlt-1 and α2M in combination with VEGF. ET-1 mRNA expression in the cells was measured by real time RT-PCR and ET-1 protein by western blot analysis. RESULTS: ET-1 expression in HMEC-1 incubated with VEGF significantly increased in time- and dose-dependent manners. Next, HMEC-1 was treated with the sFlt-1 (10-1000 ng/mL) or α2M (10-10000 ng/mL) in the presence of VEGF (10 ng/mL). We found that sFlt-1 induced a significant decrease of ET-1 expression upregulated by VEGF, while α2M did not affect the VEGF-induced ET-1 expression. CONCLUSIONS: sFLT-1 suppressed the VEGF-induced the ET-1 expression of HMEC-1. However, α2M did not show a significant effect on the ET-1 expression that was induced by VEGF. The results suggest that a certain proportion of the bound form α2M-VEGF have a biological action involved in the pathophysiology of preeclampsia.
INTRODUCTION: Soluble fms-like tyrosine kinase-1 (sFlt-1) is a vascular endothelial growth factor (VEGF) binding protein and potent antagonist of VEGF. Alpha 2 macroglobulin (α2M) is another major binding protein for circulating VEGF, which is present in human plasma at higher concentration (2-4 mg/mL) than sFlt-1. This study investigated the effects of sFlt-1 and α2M on VEGF-induced endothelin-1 (ET-1) upregulation in human microvascular endothelial cell-1 (HMEC-1). METHODS: HMEC-1 was cultured and incubated with varying concentrations of sFlt-1 and α2M in combination with VEGF. ET-1 mRNA expression in the cells was measured by real time RT-PCR and ET-1 protein by western blot analysis. RESULTS:ET-1 expression in HMEC-1 incubated with VEGF significantly increased in time- and dose-dependent manners. Next, HMEC-1 was treated with the sFlt-1 (10-1000 ng/mL) or α2M (10-10000 ng/mL) in the presence of VEGF (10 ng/mL). We found that sFlt-1 induced a significant decrease of ET-1 expression upregulated by VEGF, while α2M did not affect the VEGF-induced ET-1 expression. CONCLUSIONS: sFLT-1 suppressed the VEGF-induced the ET-1 expression of HMEC-1. However, α2M did not show a significant effect on the ET-1 expression that was induced by VEGF. The results suggest that a certain proportion of the bound form α2M-VEGF have a biological action involved in the pathophysiology of preeclampsia.
Authors: Eduardo Esteves; Vera M Mendes; Bruno Manadas; Rafaela Lopes; Liliana Bernardino; Maria José Correia; Marlene Barros; Ana Cristina Esteves; Nuno Rosa Journal: J Clin Med Date: 2022-09-22 Impact factor: 4.964