Novel Expression and Regulation of Voltage-Dependent Potassium Channels in Placentas From Women With Preeclampsia

TY - JOUR

T1 - Novel Expression and Regulation of Voltage-Dependent Potassium Channels in Placentas From Women With Preeclampsia

AU - Mistry, Hiten D.

AU - McCallum, Laura A.

AU - Kurlak, Lesia O.

AU - Greenwood, Iain A.

AU - Pipkin, Fiona Broughton

AU - Tribe, Rachel M.

PY - 2011/9

Y1 - 2011/9

N2 - Preeclampsia is associated with structural/functional alterations in placental and maternal vasculature. Voltage-dependant potassium channels encoded by KCNQ1-5 genes have been detected in several types of blood vessels where they promote vascular relaxation. Voltage-dependant potassium channel function can be modulated by KCNE1-5-encoded accessory proteins. The aim of this study was to determine whether KCNQ and KCNE genes are differentially expressed in placentas from women with preeclampsia compared with normotensive controls and to examine any differences in those who delivered preterm (<37 weeks) or term. Placental biopsies (from midway between the cord and periphery) were obtained, with consent, from white European control (n=24; term) and preeclamptic (n=22; of whom 8 delivered before 37 weeks' gestation) women. KCNQ/KCNE and GAPDH mRNA expressions were determined by quantitative RT-PCR. Protein expression/localization was assessed using immunohistochemistry. KCNQ3 and KCNE5 mRNA expressions were significantly upregulated in preeclampsia (median [interquartile range]: 1.942 [0.905 to 3.379]) versus controls (0.159 [0.088 to 0.288]; P=0.001) and exhibited a strong positive correlation with each other (P <0.001), suggesting a novel heterodimer. Enhanced protein expression of KCNQ3 and KCNE5 in preeclampsia was confirmed with localization mainly restricted to the syncytiotrophoblast. KCNQ4 and KCNE1 isoforms were suppressed in placentas from term preeclamptic women versus controls (P

AB - Preeclampsia is associated with structural/functional alterations in placental and maternal vasculature. Voltage-dependant potassium channels encoded by KCNQ1-5 genes have been detected in several types of blood vessels where they promote vascular relaxation. Voltage-dependant potassium channel function can be modulated by KCNE1-5-encoded accessory proteins. The aim of this study was to determine whether KCNQ and KCNE genes are differentially expressed in placentas from women with preeclampsia compared with normotensive controls and to examine any differences in those who delivered preterm (<37 weeks) or term. Placental biopsies (from midway between the cord and periphery) were obtained, with consent, from white European control (n=24; term) and preeclamptic (n=22; of whom 8 delivered before 37 weeks' gestation) women. KCNQ/KCNE and GAPDH mRNA expressions were determined by quantitative RT-PCR. Protein expression/localization was assessed using immunohistochemistry. KCNQ3 and KCNE5 mRNA expressions were significantly upregulated in preeclampsia (median [interquartile range]: 1.942 [0.905 to 3.379]) versus controls (0.159 [0.088 to 0.288]; P=0.001) and exhibited a strong positive correlation with each other (P <0.001), suggesting a novel heterodimer. Enhanced protein expression of KCNQ3 and KCNE5 in preeclampsia was confirmed with localization mainly restricted to the syncytiotrophoblast. KCNQ4 and KCNE1 isoforms were suppressed in placentas from term preeclamptic women versus controls (P

U2 - 10.1161/HYPERTENSIONAHA.111.173740

DO - 10.1161/HYPERTENSIONAHA.111.173740

M3 - Article

VL - 58

SP - 497

EP - 504

JO - Hypertension

JF - Hypertension

IS - 3

ER -