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Modulation of proangiogenic and antiangiogenic balance by cystathionine β‐synthase and cystathionine γ‐lyase in human placenta (911.10)
Author(s) -
Ni Xin,
Hu Tianxiao,
He Ping,
Gu Hang
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.911.10
Subject(s) - cystathionine beta synthase , placenta , cystathionine gamma lyase , placental growth factor , trophoblast , endocrinology , vascular endothelial growth factor , medicine , preeclampsia , chemistry , biology , enzyme , vegf receptors , cysteine , biochemistry , fetus , pregnancy , genetics
Imbalance release of proangiogenic and antiangiogenic factor from placenta causes maternal endothelial dysfunction which is main manifestation of preeclampsia(PE). Hydrogen sulfide (H 2 S) “the third endogenous gaseous signaling transmitter”, has been shown to have a pro‐angiogenic effect. We investigated whether H 2 S modulate the release of proangiogenic and antiangiogenic factors in human placentas. It was found that H 2 S synthesis enzymes cystathionine β‐synthase(CBS) and cystathionine γ‐lyase(CSE) were expressed in human placenta. The levels of CBS and CSE positively correlated with the levels of agiogenic factor vascular endothelial growth factor(VEGF) and inversely correlated to antiangiogenic factor soluble fms‐like tyrosine kinase 1(sFlt‐1) in placentas. H 2 S precursor L‐cysteine significantly increased VEGFA release whereas decreased sFlt‐1 release in cultured placental explants andd placental trophoblasts. The effects of H 2 S precursor could be reversed by siRNA of CBS and CSE. Moreover, H 2 S decreased miR‐200c which target VEGF and increased miR‐133b which target sFlt‐1. The level of miR‐200c was significantly increased whereas miR‐133b decreased in PE placentas. Our results suggest that H 2 S is an important factor that maintains the balance of proangiogenic factor VEGFA and antiangiogenic factor sFlt‐1 in placenta. Reduced H 2 S generation in placentas leads to imbalance release of proangiogenic and antiangiogenic factor from placenta. Grant Funding Source : Natural Science Fundation of China No.81370734