Salidroside attenuates oxidized low‑density lipoprotein‑induced endothelial cell injury via promotion of the AMPK/SIRT1 pathway

Zhao,Dongming; Sun,Xinyi; Lv,Shujie; Sun,Miying; Guo,Huatao; Zhai,Yujia; Wang,Zhi; Dai,Peng; Zheng,Lina; Ye,Mingzhe; Wang,Xinpeng

doi:10.3892/ijmm.2019.4153

Salidroside attenuates oxidized low‑density lipoprotein‑induced endothelial cell injury via promotion of the AMPK/SIRT1 pathway

Authors:
- Dongming Zhao
- Xinyi Sun
- Shujie Lv
- Miying Sun
- Huatao Guo
- Yujia Zhai
- Zhi Wang
- Peng Dai
- Lina Zheng
- Mingzhe Ye
- Xinpeng Wang
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Affiliations: Department of Cardiovascular, Affiliated Hospital of Beihua University, Jilin, Jilin 132011, P.R. China, Department of Endocrinology and Metabolism, Affiliated Hospital of Beihua University, Jilin, Jilin 132011, P.R. China
Published online on: April 1, 2019 https://doi.org/10.3892/ijmm.2019.4153
Pages: 2279-2290
Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Oxidized low‑density lipoprotein (ox‑LDL)‑induced endothelial damage contributes to the initiation and pathogenesis of atherosclerosis. Salidroside can alleviate atherosclerosis and attenuate endothelial cell injury induced by ox‑LDL. However, the mechanisms involved in this process are not fully understood. Therefore, the purpose of the present study was to investigate the role of the adenosine monophosphate‑activated protein kinase (AMPK)/sirtuin (SIRT)1 pathway in the protection of salidroside against ox‑LDL‑induced human umbilical vein endothelial cells (HUVECs) injuries. The results revealed that salidroside reverses ox‑LDL‑induced HUVECs injury as demonstrated by the upregulation of cell viability and downregulation of LDH release. In addition, salidroside increased the expression of the SIRT1 protein in ox‑LDL‑treated HUVECs. Next, it was demonstrated that SIRT1 knockdown induced by transfection with small interfering (si)RNA targeting SIRT1 (siSRT1) abolished the protection of salidroside against ox‑LDL‑induced HUVECs injuries. This was illustrated by a decrease in cell viability and an increase in LDH release, caspase‑3 activity and apoptosis rate. Furthermore, salidroside mitigated ox‑LDL‑induced reactive oxygen species production, upregulated malondialdehyde content and NADPH oxidase 2 expression and decreased superoxide dismutase and glutathione peroxidase activities, while these effects were also reversed by siSIRT1 transfection. In addition, it was demonstrated that salidroside suppressed ox‑LDL‑induced mitochondrial dysfunction as demonstrated by the increase in mitochondrial membrane potential and decreases in cytochrome c expression, and Bax/Bcl‑2 reductions. However, these effects were eliminated by SIRT1 knockdown. Finally, it was demonstrated that salidroside significantly upregulated the phosphorylated‑AMPK expression in ox‑LDL‑treated HUVECs and AMPK knockdown induced by transfection with AMPK siRNA (siAMPK) leads to elimination of the salidroside‑induced increase in cell viability and the decrease in LDH release. Notably, siAMPK transfection further decreased the expression of SIRT1. In conclusion, these results suggested that salidroside protects HUVECs against ox‑LDL injury through inhibiting oxidative stress and improving mitochondrial dysfunction, which were dependent on activating the AMPK/SIRT1 pathway.

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