Impacts of ezetimibe on PCSK9 in rats: study on the expression in different organs and the potential mechanismsReport as inadecuate




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Journal of Translational Medicine

, 13:87

First Online: 14 March 2015Received: 27 July 2014Accepted: 04 March 2015DOI: 10.1186-s12967-015-0452-x

Cite this article as: Xu, RX., Liu, J., Li, XL. et al. J Transl Med 2015 13: 87. doi:10.1186-s12967-015-0452-x

Abstract

BackgroundPrevious 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.

MethodsThirty 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.

ResultsEzetimibe 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.

ConclusionsThe 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.

KeywordsEzetimibe PCSK9 Liver Intestine Kidney Molecular mechanism Rui-Xia Xu and Jun Liu contributed equally to this work.

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Author: Rui-Xia Xu - Jun Liu - Xiao-Lin Li - Sha Li - Yan Zhang - Yan-Jun Jia - Jing Sun - Jian-Jun Li

Source: https://link.springer.com/







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