Altered redox state modulates endothelial K Ca 2.3 and K Ca 3.1 levels in normal pregnancy and preeclampsia

Shinkyu Choi, Ji Aee Kim, Hai Yan Li, Sae Jin Lee, Ye Seon Seok, Tae Hun Kim, Ki Hwan Han, Mi Hye Park, Geum Joon Cho, Suk Hyo Suh

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Aims: Altered redox state has been related to the development of normal pregnancy (NP) and preeclampsia (PE). Endothelial K Ca 2.3 and K Ca 3.1 (K Ca s) play an important role in vasodilation, and K Ca s levels are affected by oxidative stress. We investigated the mechanisms of oxidative stress-mediated K Ca s expression modulation during NP and PE. Results: Human uterine microvascular endothelial cells were incubated in serum from normal nonpregnant women (n = 13) and women with NP (n = 24) or PE (n = 15), or in vascular endothelial growth factor (VEGF), oxidized low-density lipoprotein (ox-LDL), progesterone, or estradiol-17β (E 2 )-containing medium for 24 h. NP serum elevated H 2 O 2 levels via reducing catalase and glutathione peroxidase 1 levels, thereby enhancing K Ca s levels via a H 2 O 2 /fyn/extracellular signal-regulated kinase (ERK)-mediated pathway. VEGF enhanced H 2 O 2 and K Ca s levels and K Ca 3.1 currents. K Ca s were upregulated and K Ca s activation-induced endothelium-dependent relaxation (EDR) was augmented in vessels from pregnant mice and rats. Whereas PE serum, ox-LDL, progesterone, or soluble fms-like tyrosine kinase 1 (sFlt-1) elevated superoxide levels via elevating NADPH oxidase 2 (NOX2) and NOX4 levels and reducing superoxide dismutase (SOD) 1 levels, thereby downregulating K Ca s. sFlt-1 inhibited EDR. PE serum-or progesterone-induced alterations in levels of K Ca s were reversed by polyethylene glycol-SOD, NOX inhibition, or E 2 . Innovation and Conclusions: This is the first study of how endothelial K Ca s levels are modulated during NP and PE. K Ca s were upregulated by soluble serum factors such as VEGF via H 2 O 2 generation in NP, and were downregulated by serum factors such as progesterone and ox-LDL via superoxide generation in PE, which may contribute to hemodynamic adaptations in NP or to the development of PE.

Original languageEnglish
Pages (from-to)505-519
Number of pages15
JournalAntioxidants and Redox Signaling
Volume30
Issue number4
DOIs
StatePublished - 2019

Bibliographical note

Funding Information:
This research was supported by the Basic Science Research Program through the Nation Research Foundation of Korea funded by the Ministry of Education, Science and Technology (NRF-2013R1A1A2010851, NRF-2013R1A1A2064543, 2016R1D1A1A09919073, and 2016R1D1A1A09918769) and intramural research promotion grants from Ewha Womans University, School of Medicine.

Publisher Copyright:
© 2018 Mary Ann Liebert, Inc. publishers.

Keywords

  • Ca -activated K channels
  • endothelial cells
  • preeclampsia
  • pregnancy
  • redox state

Fingerprint

Dive into the research topics of 'Altered redox state modulates endothelial K Ca 2.3 and K Ca 3.1 levels in normal pregnancy and preeclampsia'. Together they form a unique fingerprint.

Cite this