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 language | English |
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Pages (from-to) | 505-519 |
Number of pages | 15 |
Journal | Antioxidants and Redox Signaling |
Volume | 30 |
Issue number | 4 |
DOIs | |
Publication status | Published - 2019 |
Bibliographical note
Publisher Copyright:© 2018 Mary Ann Liebert, Inc. publishers.
Keywords
- Ca -activated K channels
- endothelial cells
- preeclampsia
- pregnancy
- redox state
ASJC Scopus subject areas
- Biochemistry
- Physiology
- Molecular Biology
- Clinical Biochemistry
- Cell Biology