Salidroside protects against ox-LDL-induced endothelial injury by enhancing autophagy mediated by SIRT1-FoxO1 pathway

Zhongsheng Zhu,Xiaorong Zhang,Jinyu Li

doi:10.1186/s12906-019-2526-4

Zhongsheng Zhu, Xiaorong Zhang + Show 1 more

Open Access

https://doi.org/10.1186/s12906-019-2526-4

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Abstract

BackgroundAtherosclerosis is a condition with the vascular accumulation of lipid plaques, and its main major contributing factor is endothelial injury induced by oxidized low-density lipoprotein (ox-LDL). Salidroside (SAL) is the primary active ingredient of Rhodiola rosea, and exhibits antioxidant properties on endothelial cells and alleviates atherosclerosis. However, the effect of SAL on autophagy in ox-LDL-induced vascular endothelial injury remains unclear. Here, we investigated the effect and underlying mechanisms of SAL on autophagy in human umbilical vein endothelial cells (HUVECs).MethodsHUVECs were incubated with ox-LDL to induce in vitro atherosclerosis model. The cell viability and injury were evaluated by cell counting kit-8 (CCK-8) assay and lactate dehydrogenase (LDH) release assay. The oxidative stress was evaluated by NADPH oxidase, malondialdehyde (MDA) and superoxide dismutase (SOD) activities. Immunofluorescence was performed to detect autophagy using LC3β antibody. Quantitative real-time PCR (qRT-PCR) and western blot were performed to measure the mRNA expressions of SIRT1 and Forkhead box O1 (FOXO1). Nicotinamide (NAM) and AS1842856 were used to inhibit activities of SIRT1 and FOXO1, respectively.ResultsExposure of HUVECs to ox-LDL (100 μg/mL) reduced cell viability, increased cellular MDA, and reduced SOD in a concentration-dependent manner. The pretreatment with SAL (20, 50 and 100 μM) significantly enhanced the cell viability and decreased LDH release in HUVECs exposed to ox-LDL (100 μg/mL). ox-LDL induced autophagy in HUVECs, which was further enhanced by pretreatment with SAL. However, SAL attenuated increase in oxidative stress in HUVECs induced by ox-LDL. ox-LDL reduced mRNA and protein expressions of SIRT1 and FOXO1, which could be reversed by SAL. The protective, anti-oxidative and pro-autophagic effects of SAL could be obviously abolished by cotreatment with SIRT1 inhibitor or FOXO1 inhibitor.ConclusionSalidroside shows protective effect on endothelial cell induced by ox-LDL, and the mechanisms might be related to autophagy induction via increasing SIRT1 and FoxO1 expressions.

Highlights

Atherosclerosis is a condition with the vascular accumulation of lipid plaques, and its main major contributing factor is endothelial injury induced by oxidized low-density lipoprotein
Salidroside prevented the cytotoxic activity of ox-low density lipoprotein (LDL) in human umbilical vein endothelial cells (HUVECs) In order to establish the in vitro atherosclerosis model, the HUVECs were exposed to various concentrations of oxidized low-density lipoprotein (ox-LDL) (10, 20, 50, 100 and 150 μg/mL) for 48 h
We examined the effect of SAL on endothelial cell, and HUVECs were pretreated with SAL at 20, 50, 100 μM for 2 h and exposed to ox-LDL (100 μg/mL) for further 48 h

Summary

Introduction

Atherosclerosis is a condition with the vascular accumulation of lipid plaques, and its main major contributing factor is endothelial injury induced by oxidized low-density lipoprotein (ox-LDL). The effect of SAL on autophagy in ox-LDL-induced vascular endothelial injury remains unclear. We investigated the effect and underlying mechanisms of SAL on autophagy in human umbilical vein endothelial cells (HUVECs). Atherosclerosis is characterized by accumulation of lipid plaques in vascular endothelium [1]. Endothelial injury is initial event and contributing factor of atherosclerosis, and is mainly caused by oxidized low-density lipoprotein (ox-LDL) [2]. Ox-LDL destroys the oxidation-reduction equilibrium of vascular endothelial cells and induces apoptosis of endothelial cells, contributing to endothelial injury [3]. Autophagy participates in the defense mechanism against oxidative stress, thereby preventing vascular cell apoptosis [8]. The precise role of autophagy in the treatment of atherosclerosis by various agents should be investigated in different in vitro systems and animal models

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