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Impacts of ezetimibe on PCSK9 in rats: study on the expression in different organs and the potential mechanisms

BACKGROUND: Previous studies including our group have indicated the effects of ezetimibe on increased plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) concentration, while the rapid expression in different organs and the potential molecular mechanisms for this impact have not been carefu...

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Autores principales: Xu, Rui-Xia, Liu, Jun, Li, Xiao-Lin, Li, Sha, Zhang, Yan, Jia, Yan-Jun, Sun, Jing, Li, Jian-Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4365528/
https://www.ncbi.nlm.nih.gov/pubmed/25889684
http://dx.doi.org/10.1186/s12967-015-0452-x
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author Xu, Rui-Xia
Liu, Jun
Li, Xiao-Lin
Li, Sha
Zhang, Yan
Jia, Yan-Jun
Sun, Jing
Li, Jian-Jun
author_facet Xu, Rui-Xia
Liu, Jun
Li, Xiao-Lin
Li, Sha
Zhang, Yan
Jia, Yan-Jun
Sun, Jing
Li, Jian-Jun
author_sort Xu, Rui-Xia
collection PubMed
description BACKGROUND: Previous studies including our group have indicated the effects of ezetimibe on increased plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) concentration, while the rapid expression in different organs and the potential molecular mechanisms for this impact have not been carefully evaluated. METHODS: Thirty rats were randomly divided into two groups (n = 15 for each), which were orally administrated with ezetimibe (10 mg/kg/day) or normal saline. Blood samples were obtained at day 3 after orally administration, and the PCSK9 levels were determined by ELISA. We further analyzed the mRNA expression of PCSK9, low-density lipoprotein receptor (LDLR), sterol regulator element-binding protein 2 (SREBP2), and hepatocyte nuclear factor 1 alpha (HNF-1α) by real-time PCR, as well as the protein expression by western blot, in liver, intestine and kidney respectively. RESULTS: Ezetimibe significantly increased plasma PCSK9 levels compared with control group, while there was no significant difference between the two groups with regard to lipid profile at day 3. Moreover, ezetimibe remarkably increased the expression of PCSK9, LDLR, SREBP2 and HNF-1α in liver. Enhanced expression of PCSK9, LDLR and SREBP2 protein were found in intestine and kidney, while no changes in the expression of HNF-1α were observed in intestine and kidney of rats with ezetimibe treatment. CONCLUSIONS: The data demonstrated that ezetimibe increased PCSK9 expression through the SREBP2 and HNF-1α pathways in different organs, subsequently resulting in elevated plasma PCSK9 levels prior to the alterations of lipid profile in rats.
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spelling pubmed-43655282015-03-20 Impacts of ezetimibe on PCSK9 in rats: study on the expression in different organs and the potential mechanisms Xu, Rui-Xia Liu, Jun Li, Xiao-Lin Li, Sha Zhang, Yan Jia, Yan-Jun Sun, Jing Li, Jian-Jun J Transl Med Research BACKGROUND: Previous studies including our group have indicated the effects of ezetimibe on increased plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) concentration, while the rapid expression in different organs and the potential molecular mechanisms for this impact have not been carefully evaluated. METHODS: Thirty rats were randomly divided into two groups (n = 15 for each), which were orally administrated with ezetimibe (10 mg/kg/day) or normal saline. Blood samples were obtained at day 3 after orally administration, and the PCSK9 levels were determined by ELISA. We further analyzed the mRNA expression of PCSK9, low-density lipoprotein receptor (LDLR), sterol regulator element-binding protein 2 (SREBP2), and hepatocyte nuclear factor 1 alpha (HNF-1α) by real-time PCR, as well as the protein expression by western blot, in liver, intestine and kidney respectively. RESULTS: Ezetimibe significantly increased plasma PCSK9 levels compared with control group, while there was no significant difference between the two groups with regard to lipid profile at day 3. Moreover, ezetimibe remarkably increased the expression of PCSK9, LDLR, SREBP2 and HNF-1α in liver. Enhanced expression of PCSK9, LDLR and SREBP2 protein were found in intestine and kidney, while no changes in the expression of HNF-1α were observed in intestine and kidney of rats with ezetimibe treatment. CONCLUSIONS: The data demonstrated that ezetimibe increased PCSK9 expression through the SREBP2 and HNF-1α pathways in different organs, subsequently resulting in elevated plasma PCSK9 levels prior to the alterations of lipid profile in rats. BioMed Central 2015-03-14 /pmc/articles/PMC4365528/ /pubmed/25889684 http://dx.doi.org/10.1186/s12967-015-0452-x Text en © Xu et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Xu, Rui-Xia
Liu, Jun
Li, Xiao-Lin
Li, Sha
Zhang, Yan
Jia, Yan-Jun
Sun, Jing
Li, Jian-Jun
Impacts of ezetimibe on PCSK9 in rats: study on the expression in different organs and the potential mechanisms
title Impacts of ezetimibe on PCSK9 in rats: study on the expression in different organs and the potential mechanisms
title_full Impacts of ezetimibe on PCSK9 in rats: study on the expression in different organs and the potential mechanisms
title_fullStr Impacts of ezetimibe on PCSK9 in rats: study on the expression in different organs and the potential mechanisms
title_full_unstemmed Impacts of ezetimibe on PCSK9 in rats: study on the expression in different organs and the potential mechanisms
title_short Impacts of ezetimibe on PCSK9 in rats: study on the expression in different organs and the potential mechanisms
title_sort impacts of ezetimibe on pcsk9 in rats: study on the expression in different organs and the potential mechanisms
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4365528/
https://www.ncbi.nlm.nih.gov/pubmed/25889684
http://dx.doi.org/10.1186/s12967-015-0452-x
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