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Allerkamp, HH; Bondarenko, AI; Tawfik, I; Kamali-Simsek, N; Horvat, Mercnik, M; Madreiter-Sokolowski, CT; Wadsack, C.
In vitro Examination of Piezo1-TRPV4 Dynamics: Implications for Placental Endothelial Function in Normal and Preeclamptic Pregnancies.
Am J Physiol Cell Physiol. 2024;
Doi: 10.1152/ajpcell.00794.2024
Web of Science
PubMed
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FullText_MUG
- Leading authors Med Uni Graz
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Allerkamp Hanna
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Wadsack Christian
- Co-authors Med Uni Graz
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Bondarenko Oleksandr
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Madreiter-Sokolowski Corina
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Tawfik Ines
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- Abstract:
- Mechanosensation is essential for endothelial cell (EC) function, which is compromised in early-onset preeclampsia (EPE), impacting offspring health. The ion channels Piezo-type mechanosensitive ion channel component 1 (Piezo1) and Transient receptor potential cation channel subfamily V member 4 (TRPV4) are co-regulated mechanosensors in ECs. Current evidence suggests that both channels could mediate aberrant placental endothelial function in EPE. Using isolated feto-placental ECs (fpECs) from early control (EC) and EPE pregnancies, we show functional co-expression of both channels and that Ca2+ influx and membrane depolarization in response to chemical channel activation is reduced in EPE fpECs. Downstream of channel activation, Piezo1 alone can induce phosphorylation of endothelial nitric oxide synthase (eNOS) in fpECs, while combined activation of Piezo1 and TRPV4 only affects eNOS phosphorylation in EPE fpECs. Additionally, combined activation reduces the barrier integrity of fpECs, also with a stronger effect on EPE fpECs. This implies altered Piezo1-TRPV4 co-regulation in EPE. Mechanistically, we suggest this to be driven by changes in the arachidonic acid metabolism in EPE fpECs as identified by RNA-Seq. Targeting of Piezo1 and TRPV4 might hold potential for EPE treatment options in the future.
- Find related publications in this database (Keywords)
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endothelium
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ion channels
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nitric oxide
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placenta
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preeclampsia