Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17968334_1.fastq.gz | Fastqsanger.gz | |||
| SRR17968334_2.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:CETP transfers lipids and cholesteryl esters between lipoproteins. This leads to elevated LDL-cholesterol levels. We found elevated cholesterol levels in the brains CETP transgenic animals. We wanted to test whether this is due to increased cholesterol synthesis by astrocytes 2 animals that were genotyped as wild type showed CETP transcription in our RT-qPCR (WT_1 & WT_5) and were excluded
2018-03-01 | GSE111242 | GEO
Project description:Cholesteryl ester transfer protein (CETP) transfers cholesteryl ester (CE) and triglyceride (TG) between lipoproteins, which alters lipoprotein metabolism. Hamster and human CETPs have very different preferences for CE versus TG as substrate. To assess the impact of altering CETP’s substrate preference on lipoproteins in vivo, human CETP was expressed in hamsters (Mesocricetus auratus). Chow-fed hamsters received adenoviruses expressing no CETP (Ad-Null), hamster CETP (Ad-hamster CETP) or human CETP (Ad-human CETP). High density lipoproteins were isolated from hamster plasma 6 days after adenovirus injection by ultracentrifugation as the 1.063 - 1.21 g/ml density fraction. HDL proteins were precipitated with cold acetone and subjected to LC+MS/MS analysis
2020-06-25 | PXD017998 | Pride
Project description:Pharmacogenomic studies have revealed associations between rs1967309 in the adenylyl cyclase type 9 (ADCY9) gene and clinical responses to the cholesteryl ester transfer protein (CETP) modulator dalcetrapib, however, the mechanism behind this interaction is still unknown. Here, we characterized selective signals at the locus associated with the pharmacogenomic response in human populations and we show that rs1967309 region exhibits signatures of natural selection in several human populations. Furthermore, we identified a variant in CETP, rs158477, which is in long-range linkage disequilibrium with rs1967309 in the Peruvian population. The signal is mainly seen in males, a sex-specific result that is replicated in the LIMAA cohort of over 3,400 Peruvians. We further detected interaction effects of these two SNPs with sex on cardiovascular phenotypes in the UK Biobank, in line with the sex-specific genotype associations found in Peruvians at these loci. Analyses of RNA-seq data further suggest an epistatic interaction on CETP expression levels between the two SNPs in multiple tissues. We propose that ADCY9 and CETP coevolved during recent human evolution, which points towards a biological link between dalcetrapib’s pharmacogene ADCY9 and its therapeutic target CETP.
2021-11-24 | GSE174640 | GEO
Project description:To explore the impact of cholesteryl ester transfer protein (CETP) gene on atherosclerosis-associated phenotypes, we newly generate a human CETP-transgenic (Tg[hCETP]) strain of the genetic background of spontaneously hypertensive rat (SHR). Microarray gene expression analysis was performed on the liver to examine differential regulation of lipid metabolism-related genes.
2020-01-14 | E-MTAB-7861 | biostudies-arrayexpress
Project description:Increased serum apoB and associated low density lipoprotein cholesterol (LDL) levels are well correlated with an increased risk of coronary disease. Apo E-/- and LDLr -/- mice have been extensively used for studies of coronary atherosclerosis. These animals show atherosclerotic lesions similar to those in humans, but their serum lipids are low in apoB containing LDL particles. We describe the development of a new mouse model with a human-like lipid profile. Ldlr+/- CETP+/- hemizygous mice carry a single copy of the human CETP transgene and a single copy of a LDL receptor mutation. To evaluate the apoB pathways in this mouse model, we used novel siRNAs formulated in lipid nanoparticles (LNPs). ApoB siRNAs induced up to 95% reduction of liver ApoB mRNA and serum apoB protein, and a significant lowering of serum LDL in Ldlr+/- CETP+/- mice. ApoB targeting is specific, dose dependent and shows lipid lowering effects for over three weeks. Although specific TGs were affected by ApoB KD, and the total plasma lipid levels were decreased by 70%, the overall lipid distribution did not change. Results presented here demonstrate a new mouse model for investigating additional targets within the ApoB pathways using the siRNA modality. Two oligoes specific for ApoB were used to knock down apoB expression in C57Bl6 or B6-Ldlr(tm1)Tg(APOA1-CETP) mice. Gene expression profiling was performed with Affymetrix Merck Custom Mouse 1.0 microarrays (GPL9734).
2010-11-22 | E-GEOD-23088 | biostudies-arrayexpress
Project description:Increased serum apoB and associated low density lipoprotein cholesterol (LDL) levels are well correlated with an increased risk of coronary disease. Apo E-/- and LDLr -/- mice have been extensively used for studies of coronary atherosclerosis. These animals show atherosclerotic lesions similar to those in humans, but their serum lipids are low in apoB containing LDL particles. We describe the development of a new mouse model with a human-like lipid profile. Ldlr+/- CETP+/- hemizygous mice carry a single copy of the human CETP transgene and a single copy of a LDL receptor mutation. To evaluate the apoB pathways in this mouse model, we used novel siRNAs formulated in lipid nanoparticles (LNPs). ApoB siRNAs induced up to 95% reduction of liver ApoB mRNA and serum apoB protein, and a significant lowering of serum LDL in Ldlr+/- CETP+/- mice. ApoB targeting is specific, dose dependent and shows lipid lowering effects for over three weeks. Although specific TGs were affected by ApoB KD, and the total plasma lipid levels were decreased by 70%, the overall lipid distribution did not change. Results presented here demonstrate a new mouse model for investigating additional targets within the ApoB pathways using the siRNA modality.
2010-11-22 | GSE23088 | GEO
Project description:Identification of causal genes for atherosclerosis in a segregating mouse population and validation via single-gene knockout and plaque progression mouse models. This SuperSeries is composed of the following subset Series: GSE18442: Aortic arch profiling of Ldlr knockout mice with human CETP transgene GSE18443: Aortic arch profiling of Apoe knockout mice Refer to individual Series
2010-06-23 | E-GEOD-18479 | biostudies-arrayexpress
Project description:ILLUMINATE (Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events), the phase 3 morbidity and mortality trial of torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, identified previously undescribed changes in plasma levels of potassium, sodium, bicarbonate, and aldosterone. A key question after this trial is whether the failure of torcetrapib was a result of CETP inhibition or of some other pharmacology of the molecule. The direct effects of torcetrapib and related molecules on adrenal steroid production were assessed in cell culture using the H295R as well as the newly developed HAC15 human adrenal carcinoma cell lines. Torcetrapib induced the synthesis of both aldosterone and cortisol in these two in vitro cell systems. Analysis of steroidogenic gene expression indicated that torcetrapib significantly induced the expression of CYP11B2 and CYP11B1, two enzymes in the last step of aldosterone and cortisol biosynthesis pathway, respectively. Transcription profiling indicated that torcetrapib and angiotensin II share overlapping pathways in regulating adrenal steroid biosynthesis. Hormone-induced steroid production is mainly mediated by two messengers, calcium and cAMP. An increase of intracellular calcium was observed after torcetrapib treatment, whereas cAMP was unchanged. Consistent with intracellular calcium being the key mediator of torcetrapib’s effect in adrenal cells, calcium channel blockers completely blocked torcetrapib-induced corticoid release and calcium increase. A series of compounds structurally related to torcetrapib as well as structurally distinct compounds were profiled. The results indicate that the pressor and adrenal effects observed with torcetrapib and related molecules are independent of CETP inhibition.
2009-05-02 | GSE15918 | GEO
Project description:A sex-specific evolutionary interaction between ADCY9 and CETP
| PRJNA730867 | ENA
Project description:Morgan2016 - Dynamics of cholesterol
metabolism and ageing
This model is described in the article:
Mathematically modelling the
dynamics of cholesterol metabolism and ageing.
Morgan AE, Mooney KM, Wilkinson SJ,
Pickles NA, Mc Auley MT.
BioSystems 2016 Jul; 145: 19-32
Abstract:
Cardiovascular disease (CVD) is the leading cause of
morbidity and mortality in the UK. This condition becomes
increasingly prevalent during ageing; 34.1% and 29.8% of males
and females respectively, over 75 years of age have an
underlying cardiovascular problem. The dysregulation of
cholesterol metabolism is inextricably correlated with
cardiovascular health and for this reason low density
lipoprotein cholesterol (LDL-C) and high density lipoprotein
cholesterol (HDL-C) are routinely used as biomarkers of CVD
risk. The aim of this work was to use mathematical modelling to
explore how cholesterol metabolism is affected by the ageing
process. To do this we updated a previously published
whole-body mathematical model of cholesterol metabolism to
include an additional 96 mechanisms that are fundamental to
this biological system. Additional mechanisms were added to
cholesterol absorption, cholesterol synthesis, reverse
cholesterol transport (RCT), bile acid synthesis, and their
enterohepatic circulation. The sensitivity of the model was
explored by the use of both local and global parameter scans.
In addition, acute cholesterol feeding was used to explore the
effectiveness of the regulatory mechanisms which are
responsible for maintaining whole-body cholesterol balance. It
was found that our model behaves as a hypo-responder to
cholesterol feeding, while both the hepatic and intestinal
pools of cholesterol increased significantly. The model was
also used to explore the effects of ageing in tandem with three
different cholesterol ester transfer protein (CETP) genotypes.
Ageing in the presence of an atheroprotective CETP genotype,
conferring low CETP activity, resulted in a 0.6% increase in
LDL-C. In comparison, ageing with a genotype reflective of high
CETP activity, resulted in a 1.6% increase in LDL-C. Thus, the
model has illustrated the importance of CETP genotypes such as
I405V, and their potential role in healthy ageing.
This model is hosted on
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MODEL1508170000.
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2017-06-01 | MODEL1508170000 | BioModels