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

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5 Citations (Scopus)

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
Publication statusPublished - 2019

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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    Choi, S., Kim, J. A., Li, H. Y., Lee, S. J., Seok, Y. S., Kim, T. H., Han, K. H., Park, M. H., Cho, G. J., & Suh, S. H. (2019). Altered redox state modulates endothelial K Ca 2.3 and K Ca 3.1 levels in normal pregnancy and preeclampsia Antioxidants and Redox Signaling, 30(4), 505-519. https://doi.org/10.1089/ars.2017.7038