Association of Dll4Notch and HIF-1a -VEGF Signaling in the Angiogenesis of Missed Abortion.docVIP

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Association of Dll4Notch and HIF-1a -VEGF Signaling in the Angiogenesis of Missed Abortion.doc

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Association of Dll4Notch and HIF-1a -VEGF Signaling in the Angiogenesis of Missed Abortion

AssociationofDll4/NotchandHIF-1a-VEGFSignalingin theAngiogenesisofMissedAbortion YanFang1.,ShuangYu2.,YuyanMa1,PingSun1,DaoxinMa2*,ChunyanJi2,BeihuaKong1* 1Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Ji’nan, Shandong, China, 2Department of Hematology, Qilu Hospital, Shandong University,Ji’nan,Shandong,China Abstract Background:Dll4/NotchandHIF-1a-VEGFhavebeenshowntoplayanimportantroleduringangiogenesis,butthereareno dataabouttheirrolesandassociationinmissedabortion.Inthisstudy,weinvestigatedtheassociationofDll4/Notchand HIF-1a-VEGFsignalinginmissedabortion. Methods:Womenwithmissedabortion(n=27)andhealthycontrols(n=26)wereincludedinthestudy.Real-timeReverse Transcription-PCR Analyses (RT-PCR) was used to analyze the mRNA levels of Dll4/Notch and HIF-1a-VEGF signaling molecules.TheproteinlevelforDll4wasmeasuredbyimmunohistochemistry. Results:Comparedwithinducedabortion,theexpressionofVEGFwasstatisticallyreducedwhilethelevelofVEGFR1and Notch1 was significantly up-regulated in missed abortion. Though other molecules (VEGFR2 and Dll4) were marginally higherinmissedabortion,nostatisticaldifferencewasobserved.TheexpressionofHIF-1awassignificantlyup-regulated, and close negatively correlated with VEGF in missed abortion. Both in induced abortion and missed abortion, Dll4 was positivelycorrelatedwithNotch1. Conclusions:Theearlypregnancyisinahypoxicenvironment,thismayencouragetheangiogenesis,butseverehypoxic mayinhibittheangiogenesis.AberrantDll4/NotchandHIF-1a-VEGFsignalingmayhavearoleinmissedabortion. Citation: FangY, Yu S,MaY, Sun P,MaD,etal.(2013) Associationof Dll4/Notch andHIF-1a -VEGF Signalingin the Angiogenesis of MissedAbortion. PLoS ONE8(8):e70667.doi:10.1371/journal.pone.0070667 Editor:BinHe,BaylorCollegeofMedicine,UnitedStatesofAmerica ReceivedFebruary14,2013;AcceptedJune20,2013;PublishedAugust9,2013 Copyright: ? 2013 Fang etal. This is an open-access article distributed under the terms of the Creative Commons Attribution Lic