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Preeclamptic serum and soluble fms-like tyrosine kinase-1 suppress endothelial inward rectifier potassium currents.
Theerathananon, Wuttinan; Watanapa, Wattana B; Wataganara, Tuangsit; Pratumvinit, Busadee; Rahman, Suraiya.
Afiliación
  • Theerathananon W; Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkok, 10700, Thailand. Electronic address: wutheera@gmail.com.
  • Watanapa WB; Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkok, 10700, Thailand. Electronic address: wattana.wat@mahidol.ac.th.
  • Wataganara T; Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkok, 10700, Thailand. Electronic address: twataganara@yahoo.com.
  • Pratumvinit B; Department of Clinical Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkok, 10700, Thailand. Electronic address: busadee.pra@mahidol.ac.th.
  • Rahman S; Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkok, 10700, Thailand. Electronic address: Yaya1713@gmail.com.
Placenta ; 146: 101-109, 2024 02.
Article en En | MEDLINE | ID: mdl-38241839
ABSTRACT

INTRODUCTION:

Inward rectifier K+ (Kir) channel, a major factor determining endothelial membrane potential, regulates Ca2+ influx and vasodilator release, which is impaired in preeclamptic blood vessels. Previously, human umbilical vein endothelial cell (HUVEC) Kir currents were shown to decrease after incubating in preeclamptic plasma. We aimed to demonstrate whether sFlt-1, which is high in preeclamptic blood, could inhibit Kir channel function and expression.

METHODS:

HUVECs were cultured in regular medium, regular medium with added sFlt-1, or serum from preeclampsia patients or normal pregnant women (Control, sFlt-1, PE, or NP, respectively). Using whole-cell patch clamp technique, we identified Kir currents with the Kir blocker 2 mM BaCl2 and compared the currents among groups. The expression of Kir 2.1 and 2.2 channels were determined using immunofluorescent staining.

RESULTS:

sFlt-1 and PE groups exhibited similar Kir currents, while NP group possessed significantly larger currents, similar to Control group currents. Moreover, sFlt-1 and sFlt-1/PlGF ratio showed strong negative correlation with Kir currents (r = -0.71 and -0.70, respectively; P < 0.05). There were no significant differences in mean fluorescence intensity representing Kir 2.1 and 2.2 channels expression in all four groups.

DISCUSSION:

This is the first report to demonstrate sFlt-1 inhibition against Kir currents, which could lead to maternal endothelial dysfunction and hypertension seen in preeclampsia. However, channel expression was unaffected by sFlt-1 incubation, suggesting dysfunctions of channel or other processes (e.g., membrane translocation). The present data could pave the way for novel therapies targeting sFlt-1 or Kir to alleviate hypertension in preeclampsia.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Preeclampsia / Hipertensión Tipo de estudio: Prognostic_studies Límite: Female / Humans / Pregnancy Idioma: En Revista: Placenta Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Preeclampsia / Hipertensión Tipo de estudio: Prognostic_studies Límite: Female / Humans / Pregnancy Idioma: En Revista: Placenta Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos