title: The NOX2-derived reactive oxygen species damaged endothelial nitric oxide system via suppressed BKCa/SKCa in preeclampsia.
abstract: The endothelial nitric oxide (NO) system may be damaged in preeclampsia; however, the involved mechanisms are unclear. In this study, we used primary human umbilical vein endothelial cells (HUVECs) to evaluate the endothelial NO system in preeclampsia and to determine the underlying mechanisms that are involved. We isolated and cultured HUVECs from normal and preeclamptic pregnancies and evaluated endothelial NO synthase enzyme (eNOS) expression and NO production. Whole-cell K+currents and oxidative stress were also determined in normal and preeclamptic HUVECs. Compared with normal HUVECs, eNOS expression, NO production and whole-cell K+currents in preeclamptic HUVECs were markedly decreased, whereas oxidative stress was significantly increased. The decreased K+currents were associated with damaged Ca2+-activated K+(KCa) channels, especially the large (BKCa) and small (SKCa) conductance KCa channels, and were involved in the downregulated eNOS expression in preeclamptic HUVECs. Moreover, the increased oxidative stress detected in preeclamptic HUVECs was mediated by NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 2 (NOX2)-dependent reactive oxygen species overproduction that could downregulate whole-cell K+currents, eNOS expression and NO production. Taken together, our study indicated that the increased oxidative stress in preeclamptic HUVECs could downregulate the NO system by suppressing BKCa and SKCa channels. Because the damaged NO system was closely related to endothelial dysfunction, this study provides important information to further understand the pathological process of endothelial cell dysfunction in preeclampsia.
authors.affiliation: Institute for Fetology, First Affiliated Hospital of Soochow University, Suzhou, China.|Department of Obstetrics and Gynecology, First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Institute for Fetology, First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Qinqin
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Institute for Fetology, First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Institute for Fetology, First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Xueqin
authors.initials: X
authors.lastname: Feng
authors.affiliation: Institute for Fetology, First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Institute for Fetology, First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Fan
authors.affiliation: Institute for Fetology, First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Caiping
authors.initials: C
authors.lastname: Mao
authors.affiliation: Institute for Fetology, First Affiliated Hospital of Soochow University, Suzhou, China.|Center for Perinatal Biology, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Zhice
authors.initials: Z
authors.lastname: Xu
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000235:genetics / Q000378:metabolism*; D000074662:NADPH Oxidase 2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D009569:Nitric Oxide / Q000096:biosynthesis; D018384:Oxidative Stress; D015221:Potassium Channels / Q000378:metabolism; D011225:Pre-Eclampsia; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
chemical_list: C494841:KCNMA1 protein, human; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D015221:Potassium Channels; D017382:Reactive Oxygen Species; D051640:Small-Conductance Calcium-Activated Potassium Channels; D013481:Superoxides; D009569:Nitric Oxide; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases