ABCC6- a new player in cellular cholesterol and lipoprotein metabolism?

Lipids in Health and Disease

Research

Doris Hendig¹  Patricia Kuzaj¹  Cornelius Knabbe¹  Isabel Faust¹  Joachim Kuhn¹  Mareike Dabisch-Ruthe¹  Christian Götting² 

[1] Herz- und Diabeteszentrum NRW, Institut für Laboratoriums- und Transfusionsmedizin, Universitätsklinik der Ruhr-Universität Bochum, Georgstraße 11, 32 545, Bad Oeynhausen, Germany;MVZ Labor Limbach Nürnberg, Lina-Ammon-Straße 28, 90471, Nürnberg, Germany;

关键词: Pseudoxanthoma elasticum;    ABC transporter;    ABCC6;    Cholesterol biosynthesis;    Atherosclerosis;    HMG CoA reductase;    SREBP2;    PCSK9;    LDLR;    APOE;   

DOI  :  10.1186/1476-511X-13-118

 received in 2014-05-20, accepted in 2014-07-17,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundDysregulations in cholesterol and lipid metabolism have been linked to human diseases like hypercholesterolemia, atherosclerosis or the metabolic syndrome. Many ABC transporters are involved in trafficking of metabolites derived from these pathways. Pseudoxanthoma elasticum (PXE), an autosomal-recessive disease caused by ABCC6 mutations, is characterized by atherogenesis and soft tissue calcification.MethodsIn this study we investigated the regulation of cholesterol biosynthesis in human dermal fibroblasts from PXE patients and healthy controls.ResultsGene expression analysis of 84 targets indicated dysregulations in cholesterol metabolism in PXE fibroblasts. Transcript levels of ABCC6 were strongly increased in lipoprotein-deficient serum (LPDS) and under serum starvation in healthy controls. For the first time, increased HMG CoA reductase activities were found in PXE fibroblasts. We further observed strongly elevated transcript and protein levels for the proprotein convertase subtilisin/kexin type 9 (PCSK9), as well as a significant reduction in APOE mRNA expression in PXE.ConclusionIncreased cholesterol biosynthesis, elevated PCSK9 levels and reduced APOE mRNA expression newly found in PXE fibroblasts could enforce atherogenesis and cardiovascular risk in PXE patients. Moreover, the increase in ABCC6 expression accompanied by the induction of cholesterol biosynthesis supposes a functional role for ABCC6 in human lipoprotein and cholesterol homeostasis.

【 授权许可】

Unknown   
© Kuzaj et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. 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.