<i>ABCA1</i> and <i>ABCG1</i> expressions are regulated by statins and ezetimibe in Caco-2 cells

Genvigir, Fabiana Dalla Vecchia; Rodrigues, Alice Cristina; Cerda, Álvaro; Hirata, Mário Hiroyuki; Curi, Rui; Hirata, Rosário Dominguez Crespo

doi:10.1515/dmdi.2011.101

Cited by 12 publications

(9 citation statements)

References 17 publications

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“…Indeed, the most significantly associated gene was the LDLR , which was up-regulated among patients using statin. Of the strongly correlated genes, ABCG1 was down-regulated with statin use, in line with previous reports [ 45 ]. Furthermore, sterol-C4-methyl oxidase-like (SC4MOL) and 24-dehydrocholesterol reductase ( DHCR24 , also known as seladin 1) were significantly up-regulated among statin users.…”

Section: Discussionsupporting

confidence: 91%

The Effect of Statins on Blood Gene Expression in COPD

et al. 2015

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BackgroundCOPD is currently the fourth leading cause of death worldwide. Statins are lipid lowering agents with documented cardiovascular benefits. Observational studies have shown that statins may have a beneficial role in COPD. The impact of statins on blood gene expression from COPD patients is largely unknown.ObjectiveIdentify blood gene signature associated with statin use in COPD patients, and the pathways underpinning this signature that could explain any potential benefits in COPD.MethodsWhole blood gene expression was measured on 168 statin users and 451 non-users from the ECLIPSE study using the Affymetrix Human Gene 1.1 ST microarray chips. Factor Analysis for Robust Microarray Summarization (FARMS) was used to process the expression data. Differential gene expression analysis was undertaken using the Linear Models for Microarray data (Limma) package adjusting for propensity score and surrogate variables. Similarity of the expression signal with published gene expression profiles was performed in ProfileChaser.Results25 genes were differentially expressed between statin users and non-users at an FDR of 10%, including LDLR, CXCR2, SC4MOL, FAM108A1, IFI35, FRYL, ABCG1, MYLIP, and DHCR24. The 25 genes were significantly enriched in cholesterol homeostasis and metabolism pathways. The resulting gene signature showed correlation with Huntington’s disease, Parkinson’s disease and acute myeloid leukemia gene signatures.ConclusionThe blood gene signature of statins’ use in COPD patients was enriched in cholesterol homeostasis pathways. Further studies are needed to delineate the role of these pathways in lung biology.

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Section: Discussionsupporting

confidence: 91%

The Effect of Statins on Blood Gene Expression in COPD

et al. 2015

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“…We have previously demonstrated that statins increase the levels of the microRNA miR33, which downregulates the expression of ABCA1, decreases the ABCA1 efflux-capacity of treated cells, and counteracts the effect of dalcetrapib on cholesterol efflux in cultured macrophages [42]. In addition, simvastatin and atorvastatin treatments have been shown to decrease the level of ABCA1 mRNA in vitro and in circulating human blood cells [25,26]. In the present study, we observed a reduction in ABCA1 mRNA in the intestine of simvastatin-treated hamsters (see Supplementary Material) which was associated with a decrease in plasma and liver lutein and zeaxanthin levels.…”

Section: Discussionmentioning

confidence: 99%

“…We next characterized the response of hamsters to dietary lutein and zeaxanthin by measuring lutein and zeaxanthin plasma levels and liver accumulation in hamsters treated with the liver X receptor (LXR) agonist T0901317, which increases ABCA1 transcription and protein levels in most tissues including liver and intestine [24]. Since statins decrease ABCA1 expression in human intestinal Caco-2 cells [25] by cholesterol depletion, as well as decreasing oxysterol levels and increasing miR33 [26], we investigated the effect of simvastatin on plasma and liver lutein and zeaxanthin levels. The CETP modulator dalcetrapib enhances the activity of CETP, thus favoring lipid-poor apoA1 formation, whereas non-selective, complete CETP inhibitors such as anacetrapib blunt this process [23].…”

Section: Introductionmentioning

confidence: 99%

Effect of Compounds Affecting ABCA1 Expression and CETP Activity on the HDL Pathway Involved in Intestinal Absorption of Lutein and Zeaxanthin

Niesor

Chaput

Mary

et al. 2014

Lipids

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The antioxidant xanthophylls lutein and zeaxanthin are absorbed from the diet in a process involving lipoprotein formation. Selective mechanisms exist for their intestinal uptake and tissue-selective distribution, but these are poorly understood. We investigated the role of high-density lipoprotein (HDL), apolipoprotein (apo) A1 and ATP-binding cassette transporter (ABC) A1 in intestinal uptake of lutein in a human polarized intestinal cell culture and a hamster model. Animals received dietary lutein and zeaxanthin and either a liver X receptor (LXR) agonist or statin, which up- or down-regulate intestinal ABCA1 expression, respectively. The role of HDL was studied following treatment with the cholesteryl ester transfer protein (CETP) modulator dalcetrapib or the CETP inhibitor anacetrapib. In vitro, intestinal ABCA1 at the basolateral surface of enterocytes transferred lutein and zeaxanthin to apoA1, not to mature HDL. In hamsters, plasma lutein and zeaxanthin levels were markedly increased with the LXR agonist and decreased with simvastatin. Dalcetrapib, but not anacetrapib, increased plasma and liver lutein and zeaxanthin levels. ABCA1 expression and apoA1 acceptor activity are important initial steps in intestinal uptake and maintenance of lutein and zeaxanthin levels by an HDL-dependent pathway. Their absorption may be improved by physiological and pharmacological interventions affecting HDL metabolism.

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“…Estes dados estão apresentados como Apêndice 1 e foram publicados em artigos de nosso grupo de pesquisa (RODRIGUES et al, 2009a;RODRIGUES et al, 2009b;GENVIGIR et al, 2010;CERDA et al, 2011;GENVIGIR et al, 2011). …”

Section: Estudos In Vitrounclassified

Efeitos de hipolipemiantes sobre a expressão de CYP3A4 e CYP3A5 in vitro e in vivo

Willrich¹

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ABCA1 and ABCG1 expressions are regulated by statins and ezetimibe in Caco-2 cells

Abstract: Our findings reveal that, at the concentrations studied, statins isolated or combined with ezetimibe, but not ezetimibe alone, downregulate ABCA1 mRNA expression in Caco-2 cells. Moreover, simvastatin combined with ezetimibe treatment also decrease the ABCG1 levels in these cells.

Cited by 12 publications

References 17 publications

The Effect of Statins on Blood Gene Expression in COPD

The Effect of Statins on Blood Gene Expression in COPD

Effect of Compounds Affecting ABCA1 Expression and CETP Activity on the HDL Pathway Involved in Intestinal Absorption of Lutein and Zeaxanthin

Efeitos de hipolipemiantes sobre a expressão de CYP3A4 e CYP3A5 in vitro e in vivo

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