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Placenta. 2014 Jan;35(1):64-9. doi: 10.1016/j.placenta.2013.09.008. Epub 2013 Sep 25.

Effects of sFlt-1 and alpha 2-macroglobulin on vascular endothelial growth factor-induced endothelin-1 upregulation in human microvascular endothelial cells.

Author information

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.

KEYWORDS:

Endothelin-1; Preeclampsia; sFlt-1; α(2)-macroglobulin

PMID:
24231447
DOI:
10.1016/j.placenta.2013.09.008
[Indexed for MEDLINE]

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