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Article Open Access

Rosuvastatin protects against endothelial cell apoptosis in vitro and alleviates atherosclerosis in ApoE‑/‑ mice by suppressing endoplasmic reticulum stress

  • Authors:
    • Jianan Geng
    • Huali Xu
    • Wenwen Fu
    • Xiaofeng Yu
    • Guoliang Xu
    • Hongyan Cao
    • Guangzhu Lin
    • Dayun Sui
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Cardiovascular Medicine, the Eastern Division of First Hospital, Jilin University, Changchun, Jilin 130031, P.R. China
    Copyright: © Geng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 550-560
    |
    Published online on: May 8, 2020
       https://doi.org/10.3892/etm.2020.8733
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Abstract

The development of abnormal lipid‑induced atherosclerosis is initiated with endothelial cell apoptosis. Vascular endothelial cells possess highly developed endoplasmic reticulum (ER), which is involved in lipid metabolism, indicating that ER stress may contribute chiefly to the induction of endothelial cell apoptosis. Based on its ability to reduce cholesterol levels, rosuvastatin may play an endothelial and vascular protective role by regulating ER stress. In the present study, the involvement of the inhibition of the ER stress‑induced endothelial injury was investigated in combination with the lipid lowering effects of rosuvastatin. This compound can be used to inhibit cholesterol synthesis in atherosclerosis. Rosuvastatin decreased the apoptotic rates of human umbilical vascular endothelial cells (HUVECs) that had been stimulated with ox‑low density lipoprotein (LDL) in vitro and repressed the mRNA levels of CHOP, sXBP1 and caspase‑12, and decreased caspase‑12 activity, as well as the content of glucose‑regulated protein 78 (GRP78), phosphorylated (p)‑protein kinase RNA‑like ER kinase (PERK), p‑inositol‑requiring protein 1α (IRE1α) and p‑eIF2α proteins. In addition, ApoE‑/‑ mice were fed with atherogenic chow for 8 weeks for atherosclerosis induction and rosuvastatin was provided by intragastric administration for an additional 4 weeks. Subsequently, the atherosclerotic plaque formation in the aorta was evaluated by Oil Red O and hematoxylin and eosin staining, and the serum LDL, high‑density lipoprotein, total cholesterol (TC) and triacylglycerol (TG) levels were measured. In addition, the induction of apoptosis of endothelial cells and the expression levels of GRP78, p‑PERK, p‑IRE1α and p‑eIF2α were assessed in the aorta. Rosuvastatin repressed atherosclerotic plaque formation and endothelial apoptosis in the aorta and decreased LDL and TG levels in the serum, as determined by in vivo results. Furthermore, it downregulated the expression levels of protein chaperone GRP78, p‑PERK, p‑IRE1α and p‑eIF2α in the aortic intima. The data indicated that rosuvastatin could protect HUVECs from ER stress‑induced apoptosis triggered by oxidized LDL. It could also inhibit atherosclerosis formation in ApoE‑/‑ mice aorta by regulating the PERK/eIF2α/C/EBPα‑homologous protein and IRE1α/sXBP1 signaling pathways. Taken collectively, the present study demonstrated the preventive and therapeutic effects of rosuvastatin in protecting from the development of endothelial cell dysfunction diseases.
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Copy and paste a formatted citation
Spandidos Publications style
Geng J, Xu H, Fu W, Yu X, Xu G, Cao H, Lin G and Sui D: Rosuvastatin protects against endothelial cell apoptosis in vitro and alleviates atherosclerosis in ApoE‑/‑ mice by suppressing endoplasmic reticulum stress. Exp Ther Med 20: 550-560, 2020.
APA
Geng, J., Xu, H., Fu, W., Yu, X., Xu, G., Cao, H. ... Sui, D. (2020). Rosuvastatin protects against endothelial cell apoptosis in vitro and alleviates atherosclerosis in ApoE‑/‑ mice by suppressing endoplasmic reticulum stress. Experimental and Therapeutic Medicine, 20, 550-560. https://doi.org/10.3892/etm.2020.8733
MLA
Geng, J., Xu, H., Fu, W., Yu, X., Xu, G., Cao, H., Lin, G., Sui, D."Rosuvastatin protects against endothelial cell apoptosis in vitro and alleviates atherosclerosis in ApoE‑/‑ mice by suppressing endoplasmic reticulum stress". Experimental and Therapeutic Medicine 20.1 (2020): 550-560.
Chicago
Geng, J., Xu, H., Fu, W., Yu, X., Xu, G., Cao, H., Lin, G., Sui, D."Rosuvastatin protects against endothelial cell apoptosis in vitro and alleviates atherosclerosis in ApoE‑/‑ mice by suppressing endoplasmic reticulum stress". Experimental and Therapeutic Medicine 20, no. 1 (2020): 550-560. https://doi.org/10.3892/etm.2020.8733
Copy and paste a formatted citation
x
Spandidos Publications style
Geng J, Xu H, Fu W, Yu X, Xu G, Cao H, Lin G and Sui D: Rosuvastatin protects against endothelial cell apoptosis in vitro and alleviates atherosclerosis in ApoE‑/‑ mice by suppressing endoplasmic reticulum stress. Exp Ther Med 20: 550-560, 2020.
APA
Geng, J., Xu, H., Fu, W., Yu, X., Xu, G., Cao, H. ... Sui, D. (2020). Rosuvastatin protects against endothelial cell apoptosis in vitro and alleviates atherosclerosis in ApoE‑/‑ mice by suppressing endoplasmic reticulum stress. Experimental and Therapeutic Medicine, 20, 550-560. https://doi.org/10.3892/etm.2020.8733
MLA
Geng, J., Xu, H., Fu, W., Yu, X., Xu, G., Cao, H., Lin, G., Sui, D."Rosuvastatin protects against endothelial cell apoptosis in vitro and alleviates atherosclerosis in ApoE‑/‑ mice by suppressing endoplasmic reticulum stress". Experimental and Therapeutic Medicine 20.1 (2020): 550-560.
Chicago
Geng, J., Xu, H., Fu, W., Yu, X., Xu, G., Cao, H., Lin, G., Sui, D."Rosuvastatin protects against endothelial cell apoptosis in vitro and alleviates atherosclerosis in ApoE‑/‑ mice by suppressing endoplasmic reticulum stress". Experimental and Therapeutic Medicine 20, no. 1 (2020): 550-560. https://doi.org/10.3892/etm.2020.8733
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