Atorvastatin inhibits endoplasmic reticulum stress through AMPK signaling pathway in atherosclerosis in mice

Xiong,Wangqiong; Fei,Minzhong; Wu,Chuntao; Wang,Wei; Luo,Rong; Shen,Liping; Zhang,Zheng

doi:10.3892/etm.2019.8379

March-2020 Volume 19 Issue 3

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March-2020 Volume 19 Issue 3

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Atorvastatin inhibits endoplasmic reticulum stress through AMPK signaling pathway in atherosclerosis in mice

Authors:
- Wangqiong Xiong
- Minzhong Fei
- Chuntao Wu
- Wei Wang
- Rong Luo
- Liping Shen
- Zheng Zhang
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Affiliations: ECG Room, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai 201700, P.R. China, Cardiovascular Department, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai 201700, P.R. China

Copyright: © Xiong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 2266-2272
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Published online on: December 27, 2019

https://doi.org/10.3892/etm.2019.8379
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Abstract

Effect of atorvastatin inhibition of endoplasmic reticulum stress and amelioration of atherosclerosis through AMPK pathway were studied. Eight‑week‑old male apolipoprotein E‑deficient (ApoE‑/‑) mice were fed with high‑fat diet for 2 weeks and randomly divided into two groups: Atorvastatin treatment group was given atorvastatin (5 mg/kg/day) injection for a total of 6 weeks; control group was given the same dose of PBS through intraperitoneal injection for a total of 6 weeks. H&E staining was used to detect plaque size; immunohistochemical staining was used to detect T cells, macrophages and phospho‑protein kinase‑like ER kinase (phospho‑PERK) in localized plaques. Proteins were extracted from mouse thoracic and abdominal aortic tissues. Western blot analysis was used to detect the protein expression levels of endoplasmic reticulum stress‑related molecules phospho‑eukaryotic initiation factor‑2α (p‑eIF2α), eukaryotic initiation factor (eIF2a), and sliced x‑box binding protein 1 (sXBP‑1). Cultured human umbilical vein endothelial cells (HUVECs), induced endoplasmic reticulum stress with human oxidized low density lipoprotein (ox‑LDL), were treated with atorvastatin, AMPK agonist 5‑amino‑4‑imidazolecarboxamide riboside‑I‑β‑D‑ribofuranoside (AICAR) and AMPK‑DN that expressed a dominant‑negative mutant of AMPK. Western blot analysis was used to test the expression levels of endoplasmic reticulum stress‑related molecules p‑elF2a and sXBP‑1. The area of aortic plaques in atorvastatin group was obviously decreased, and the infiltrations of CD3+ T cells and macrophages in the localized plaques were reduced. The endoplasmic reticulum stress‑related proteins sXBP‑1 and p‑eIF2a were significantly reduced. The results of immunohistochemistry also showed a significant decrease in the level of phospho‑PERK (p‑PERK) in atorvastatin group. The results in ox‑LDL‑induced HUVECs showed that atorvastatin inhibited ox‑LDL‑induced endoplasmic reticulum stress, and the AMPK agonist AICAR also had the same effect, which was offset by DN‑AMPK treatment. Atorvastatin inhibits ER stress both in vitro and in vivo and this protective effect is mediated by AMPK activation.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Atorvastatin inhibits endoplasmic reticulum stress through AMPK signaling pathway in atherosclerosis in mice

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