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Arginase controls soluble vascular endothelial growth factor receptor 1 (sFlt1) to maintain pregnancy homeostasis
- Source :
- Biochemical and biophysical research communications. 499(2)
- Publication Year :
- 2018
-
Abstract
- Excessive soluble fms-like tyrosine kinase-1 (sFlt-1) has been strongly implicated in preeclampsia. An increase in the serum sFlt-1 level occurs before the onset of preeclampsia, and the sFlt-1 level is already higher in women who are predisposed to preeclampsia than in normotensive pregnant women. This study aimed to investigate the relation between arginase and sFlt-1 in the plasma of preeclamptic women and normotensive pregnant women. We suggested that a regulatory mechanism exists that suppresses the level of sFlt-1. The relationship between arginase, one of the nitric oxide (NO) modulators, and sFlt-1 was examined. First, the pregnant women were divided into 4 groups: group 1, sFlt-16000 pg/ml and arginase activity110 U/L; group 2, sFlt-1 ≥6000 pg/ml and arginase activity110 U/L; group 3, sFlt-1 ≥6000 pg/ml and arginase activity ≥110 U/L; and group 4, sFlt-16000 pg/ml and arginase activity ≥110 U/L. Groups 2 and 3 comprised preeclamptic women. The preeclampsia/normotensive ratio increased from groups 1 to 3. Under the higher sFlt-1 condition, lower arginase activity was associated with lower occurrence of preeclampsia. Next, in human umbilical endothelial vein cells (HUVECs), a slightly higher concentration of sFlt-1, as in group 2, reduced arginase expression and arginase activity, and S-(2-boronoethyl)-l-cysteine (BEC; arginase inhibitor) impaired sFlt-1 secretion. In contrast, a higher level of sFlt-1 increased arginase expression and activity in HUVECs, as in group 3. These results showed that arginase controlled sFlt-1 elevation to some extent. In conclusion, our results suggest the existence of a mechanism to maintain the level of sFlt-1. Soluble Flt-1 negatively regulated itself against increasing serum sFlt-1 in preeclampsia. Moreover, this study revealed that arginase inhibitors are a potential treatment option for preeclampsia.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Biophysics
030204 cardiovascular system & hematology
Transfection
Biochemistry
Nitric oxide
Preeclampsia
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Pre-Eclampsia
Pregnancy
Internal medicine
medicine
Human Umbilical Vein Endothelial Cells
Homeostasis
Humans
Secretion
Tyrosine
Molecular Biology
reproductive and urinary physiology
Vascular Endothelial Growth Factor Receptor-1
Arginase
business.industry
Pregnancy Outcome
Cell Biology
medicine.disease
Boronic Acids
Recombinant Proteins
030104 developmental biology
Endocrinology
chemistry
Solubility
embryonic structures
Female
business
Cysteine
Subjects
Details
- ISSN :
- 10902104
- Volume :
- 499
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Biochemical and biophysical research communications
- Accession number :
- edsair.doi.dedup.....53f521a332de9796c4994f74e77473c6