Elevation of hypertonicity‑induced protein NFAT5 promotes apoptosis of human umbilical vein endothelial cells through the NF‑κB pathway

Xie,Xupin; Huang,Changpin; Xu,Dong; Liu,Yongchang; Hu,Mengxiao; Long,Jianyun; Fang,Xin

doi:10.3892/mmr.2021.11823

Elevation of hypertonicity‑induced protein NFAT5 promotes apoptosis of human umbilical vein endothelial cells through the NF‑κB pathway

Authors:
- Xupin Xie
- Changpin Huang
- Dong Xu
- Yongchang Liu
- Mengxiao Hu
- Jianyun Long
- Xin Fang
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Affiliations: Department of Vascular Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China
Published online on: January 4, 2021 https://doi.org/10.3892/mmr.2021.11823
Article Number: 184

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Abstract

Abdominal aortic aneurysm (AAA) is a great threat to the health of elder (>50 years old) individuals. High salt intake is considered to raise the risk of AAA but the underlying mechanism remains to be elucidated. As endothelial dysfunction in the abdominal aorta is strongly associated with AAA, the present study hypothesized that high salt led to AAA by inducing apoptosis of endothelial cells. The present study verified that hypertonic medium with excess sodium chloride induced apoptosis of human umbilical vein endothelial cells (HUVECs), a commonly used cell model to study aortic endothelial cells. Further mechanism studies suggested that hypertonic conditions elevated the expression of nuclear factor of activated T cells 5 (NFAT5) and a high level of NFAT5 was capable of inducing apoptosis of HUVECs. In the investigation of downstream signals of NFAT5, it was identified that either hypertonic conditions or NFAT5 overexpression promoted the activity of NF‑κB signaling pathway and subsequently suppressed the expression of anti‑apoptotic protein Bcl‑2. Thus, the present study demonstrated a novel mechanism by which high salt induced apoptosis of endothelial cells by enhancing the NFAT5‑NF‑κB signaling pathway. These findings will extend our knowledge about the pathogenesis of AAA and provide potential drug targets for the treatment of AAA.

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