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Quercetin protects against atherosclerosis by regulating the expression of PCSK9, CD36, PPARγ, LXRα and ABCA1

The aim of this study was to investigate the mechanisms through which quercetin protects against atherosclerosis (AS) in apoE(−/−) mice by regulating the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9), cluster of differentiation 36 (CD36), peroxisome proliferator-activated recep...

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Autores principales: Jia, Qingling, Cao, Hui, Shen, Dingzhu, Li, Shanshan, Yan, Li, Chen, Chuan, Xing, Sanli, Dou, Fangfang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658003/
https://www.ncbi.nlm.nih.gov/pubmed/31524223
http://dx.doi.org/10.3892/ijmm.2019.4263
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author Jia, Qingling
Cao, Hui
Shen, Dingzhu
Li, Shanshan
Yan, Li
Chen, Chuan
Xing, Sanli
Dou, Fangfang
author_facet Jia, Qingling
Cao, Hui
Shen, Dingzhu
Li, Shanshan
Yan, Li
Chen, Chuan
Xing, Sanli
Dou, Fangfang
author_sort Jia, Qingling
collection PubMed
description The aim of this study was to investigate the mechanisms through which quercetin protects against atherosclerosis (AS) in apoE(−/−) mice by regulating the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9), cluster of differentiation 36 (CD36), peroxisome proliferator-activated receptor γ (PPARγ), liver X receptor α (LXRα) and ATP binding cassette transporter A1 (ABCA1). We established an animal model of high-fat diet induced AS using apoE(−/−) mice. H&E, Oil Red O and Masson's trichrome staining were performed on aortic sinus and liver tissue sections to evaluate the histopathology, lipid accumulation and collagen deposition, respectively. Filipin staining was performed to detect free cholesterol (FC) in the aortic sinus. ELISA was performed to measure the serum levels of lipids including total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) and oxidized low-density lipoprotein (oxLDL), as well as the levels of inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10. Western blot analysis was performed to analyze the protein expression levels of PCSK9, CD36, PPARγ, LXRα and ABCA1 in both the aorta and liver tissue. H&E staining revealed the presence of atherosclerotic plaques in the aortic sinus. Oil Red O staining revealed the existence of massive red-stained lipids in the aortic sinus and Masson's trichrome staining revealed decreased collagen fibers and increased plaque instability. Filipin staining revealed that free cholesterol levels in the aorta sinus were increased. In addition, H&E staining suggested hepatocyte structural disorder in the model group, and Oil Red O staining revealed a cytoplasm filled with lipid droplets, which contained a large amount of red-stained lipids. Masson's trichrome staining revealed that the liver tissue of the model group had fewer collagen fibers compared with that of the control group. Moreover, the mice in the model group had higher serum TC, LDL-C, oxLDL, TNF-α and IL-6 levels, and lower IL-10 levels. The protein expression levels of PCSK9 and CD36 were increased, while those of PPARγ, LXRα and ABCA1 were decreased in the aortas and livers of the model group mice. However, treatment with quercetin attenuated all these effects. On the whole, these results demonstrate that quercetin prevents the development of AS in apoE(−/−) mice by regulating the expression of PCSK9, CD36, PPARγ, LXRα and ABCA1.
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spelling pubmed-66580032019-08-07 Quercetin protects against atherosclerosis by regulating the expression of PCSK9, CD36, PPARγ, LXRα and ABCA1 Jia, Qingling Cao, Hui Shen, Dingzhu Li, Shanshan Yan, Li Chen, Chuan Xing, Sanli Dou, Fangfang Int J Mol Med Articles The aim of this study was to investigate the mechanisms through which quercetin protects against atherosclerosis (AS) in apoE(−/−) mice by regulating the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9), cluster of differentiation 36 (CD36), peroxisome proliferator-activated receptor γ (PPARγ), liver X receptor α (LXRα) and ATP binding cassette transporter A1 (ABCA1). We established an animal model of high-fat diet induced AS using apoE(−/−) mice. H&E, Oil Red O and Masson's trichrome staining were performed on aortic sinus and liver tissue sections to evaluate the histopathology, lipid accumulation and collagen deposition, respectively. Filipin staining was performed to detect free cholesterol (FC) in the aortic sinus. ELISA was performed to measure the serum levels of lipids including total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) and oxidized low-density lipoprotein (oxLDL), as well as the levels of inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10. Western blot analysis was performed to analyze the protein expression levels of PCSK9, CD36, PPARγ, LXRα and ABCA1 in both the aorta and liver tissue. H&E staining revealed the presence of atherosclerotic plaques in the aortic sinus. Oil Red O staining revealed the existence of massive red-stained lipids in the aortic sinus and Masson's trichrome staining revealed decreased collagen fibers and increased plaque instability. Filipin staining revealed that free cholesterol levels in the aorta sinus were increased. In addition, H&E staining suggested hepatocyte structural disorder in the model group, and Oil Red O staining revealed a cytoplasm filled with lipid droplets, which contained a large amount of red-stained lipids. Masson's trichrome staining revealed that the liver tissue of the model group had fewer collagen fibers compared with that of the control group. Moreover, the mice in the model group had higher serum TC, LDL-C, oxLDL, TNF-α and IL-6 levels, and lower IL-10 levels. The protein expression levels of PCSK9 and CD36 were increased, while those of PPARγ, LXRα and ABCA1 were decreased in the aortas and livers of the model group mice. However, treatment with quercetin attenuated all these effects. On the whole, these results demonstrate that quercetin prevents the development of AS in apoE(−/−) mice by regulating the expression of PCSK9, CD36, PPARγ, LXRα and ABCA1. D.A. Spandidos 2019-09 2019-07-03 /pmc/articles/PMC6658003/ /pubmed/31524223 http://dx.doi.org/10.3892/ijmm.2019.4263 Text en Copyright: © Jia et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Jia, Qingling
Cao, Hui
Shen, Dingzhu
Li, Shanshan
Yan, Li
Chen, Chuan
Xing, Sanli
Dou, Fangfang
Quercetin protects against atherosclerosis by regulating the expression of PCSK9, CD36, PPARγ, LXRα and ABCA1
title Quercetin protects against atherosclerosis by regulating the expression of PCSK9, CD36, PPARγ, LXRα and ABCA1
title_full Quercetin protects against atherosclerosis by regulating the expression of PCSK9, CD36, PPARγ, LXRα and ABCA1
title_fullStr Quercetin protects against atherosclerosis by regulating the expression of PCSK9, CD36, PPARγ, LXRα and ABCA1
title_full_unstemmed Quercetin protects against atherosclerosis by regulating the expression of PCSK9, CD36, PPARγ, LXRα and ABCA1
title_short Quercetin protects against atherosclerosis by regulating the expression of PCSK9, CD36, PPARγ, LXRα and ABCA1
title_sort quercetin protects against atherosclerosis by regulating the expression of pcsk9, cd36, pparγ, lxrα and abca1
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658003/
https://www.ncbi.nlm.nih.gov/pubmed/31524223
http://dx.doi.org/10.3892/ijmm.2019.4263
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