Effects of sFlt-1 and alpha 2-macroglobulin on vascular endothelial growth factor-induced endothelin-1 upregulation in human microvascular endothelial cells.
BACKGROUND
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.
Department of Obstetrics and Gynecology, College of Medicine, Korea University, Seoul, South Korea.
K W
KW
Yi
Department of Obstetrics and Gynecology, Bundang CHA University hospital, Gyeonggi, South Korea. Electronic address: aa2346@chamc.co.kr.
S H
SH
Jung
Department of Obstetrics and Gynecology, College of Medicine, Korea University, Seoul, South Korea.
G J
GJ
Cho
Department of Obstetrics and Gynecology, Kyung Hee University hospital, Seoul, South Korea.
H J
HJ
Seol
Department of Obstetrics and Gynecology, College of Medicine, Korea University, Seoul, South Korea.
S C
SC
Hong
Department of Obstetrics and Gynecology, College of Medicine, Korea University, Seoul, South Korea. Electronic address: mjohmd@korea.ac.kr.
M J
MJ
Oh
Department of Obstetrics and Gynecology, College of Medicine, Korea University, Seoul, South Korea.
H J
HJ
Kim
D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D019332:Endothelin-1 / Q000096:biosynthesis; D005260:Female; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood / Q000494:pharmacology*; D000511:alpha-Macroglobulins / Q000378:metabolism / Q000494:pharmacology*
D019332:Endothelin-1; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D000511:alpha-Macroglobulins; D040281:Vascular Endothelial Growth Factor Receptor-1
Endothelin-1; Preeclampsia; sFlt-1; α(2)-macroglobulin