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https://www.readbyqxmd.com/read/28542805/downregulation-of-cholesteryl-ester-transfer-protein-by-glucocorticoids-a-randomized-study-on-hdl
#1
Jorien Werumeus Buning, Lidya G Dimova, Frank G Perton, Uwe J F Tietge, André P van Beek, Robin P F Dullaart
BACKGROUND: High density lipoprotein (HDL) cholesterol is not decreased in hypercortisolism despite high triglycerides, which may be ascribed to effects on the cholesteryl ester transfer protein (CETP) pathway. We explored if CETP mRNA expression is modulated by glucocorticoid treatment in vitro. Effects of doubling the hydrocortisone (HCT) replacement dose on plasma CETP activity and HDL characteristics were tested in patients with secondary adrenal insufficiency. MATERIALS AND METHODS: Human THP-1 macrophages were incubated with corticosterone in vitro in the presence or absence of a liver X receptor (LXR) agonist, followed by determination of CETP mRNA levels by quantitative real-time PCR...
May 24, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28539666/replication-and-fine-mapping-of-genetic-predictors-of-lipid-traits-in-african-americans
#2
QiPing Feng, Wei-Qi Wei, Rebecca T Levinson, Jonathan D Mosley, C Michael Stein
Circulating lipid concentrations are among the strongest modifiable risk factors for coronary artery disease (CAD). Most genetic studies have focused on Caucasian populations with little information available for populations of African ancestry. Using a cohort of ~2800 African-Americans (AAs) from a biobank at Vanderbilt University (BioVU), we sought to trans-ethnically replicate genetic variants reported by the Global Lipids Genetics Consortium to be associated with lipid traits in Caucasians, followed by fine-mapping those loci using all available variants on the MetaboChip...
May 25, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28515138/dalcetrapib-and-anacetrapib-differently-impact-hdl-structure-and-function-in-rabbits-and-monkeys
#3
Mathieu R Brodeur, David Rhainds, Daniel Charpentier, Téodora Mihalache-Avram, Mélanie Mecteau, Geneviève Brand, Evelyne Chaput, Anne Perez, Eric J Niesor, Eric Rhéaume, Cyrille Maugeais, Jean-Claude Tardif
Inhibition of cholesteryl ester transfer protein (CETP) increases high density lipoprotein cholesterol (HDL-C) levels. However, circulating CETP level varies and the impact of its inhibition in species with high CETP levels on HDL structure and function remains poorly characterized. This study investigated the effects of dalcetrapib and anacetrapib, the two CETP inhibitors (CETPi) currently tested in large clinical outcome trials, on HDL particle subclass distribution and cholesterol efflux capacity of serum in rabbits and monkeys...
May 17, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28506971/protein-truncating-variants-at-the-cholesteryl-ester-transfer-protein-gene-and-risk-for-coronary-heart-disease
#4
Akihiro Nomura, Hong-Hee Won, Amit V Khera, Fumihiko Takeuchi, Kaoru Ito, Shane McCarthy, Connor A Emdin, Derek Klarin, Pradeep Natarajan, Seyedeh M Zekavat, Namrata Gupta, Gina M Peloso, Ingrid B Borecki, Tanya M Teslovich, Rosanna Asselta, Stefano Duga, Piera A Merlini, Adolfo Correa, Thorsten Kessler, James G Wilson, Matthew J Bown, Alistair S Hall, Peter S Braund, David J Carey, Michael F Murray, H L Kirchner, Joseph B Leader, Daniel R Lavage, J N Manus, Dustin N Hartzel, Nilesh J Samani, Heribert Schunkert, Jaume Marrugat, Roberto Elosua, Ruth McPherson, Martin Farrall, Hugh Watkins, Jyh-Ming Jimmy Juang, Chao A Hsiung, Shih-Yi Lin, Jun-Sing Wang, Hayato Tada, Masa-Aki Kawashiri, Akihiro Inazu, Masakazu Yamagishi, Tomohiro Katsuya, Eitaro Nakashima, Masahiro Nakatochi, Ken Yamamoto, Mitsuhiro Yokota, Yukihide Momozawa, Jerome I Rotter, Eric S Lander, Daniel J Rader, John N Danesh, Diego Ardissino, Stacey B Gabriel, Cristen J Willer, Gonçalo Abecasis, Danish Saleheen, Michiaki Kubo, Norihiro Kato, Yii-Der I Chen, Frederick Dewey, Sekar Kathiresan
Rationale: Therapies which inhibit cholesteryl ester transfer protein (CETP) have failed to demonstrate a reduction in risk for coronary heart disease (CHD). Human deoxyribonucleic acid sequence variants that truncate the CETP gene may provide insight into the efficacy of CETP inhibition. Objective: To test whether protein truncating variants (PTVs) at the CETP gene were associated with plasma lipid levels and CHD. Methods and Results: We sequenced the exons of the CETP gene in 58,469 participants from 12 case-control studies (18,817 CHD cases, 39,652 CHD-free controls)...
May 15, 2017: Circulation Research
https://www.readbyqxmd.com/read/28501703/xanthohumol-a-hop-derived-prenylated-flavonoid-promotes-macrophage-reverse-cholesterol-transport
#5
Hiroshi Hirata, Harumi Uto-Kondo, Masatsune Ogura, Makoto Ayaori, Kazusa Shiotani, Ami Ota, Youichi Tsuchiya, Katsunori Ikewaki
Xanthohumol, a prominent prenyl flavonoid from the hop plant (Humulus lupulus L.), is suggested to be antiatherogenic since it reportedly increases high-density lipoprotein (HDL) cholesterol levels. It is not clear whether xanthohumol promotes reverse cholesterol transport (RCT), the most important antiatherogenic property of HDL; therefore, we investigated the effects of xanthohumol on macrophage-to-feces RCT using a hamster model as a CETP-expressing species. In vivo RCT experiments showed that xanthohumol significantly increased fecal appearance of the tracer derived from intraperitoneally injected [(3)H]-cholesterol-labeled macrophages...
April 22, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28456421/mendelian-randomization-implicates-high-density-lipoprotein-cholesterol-associated-mechanisms-in-etiology-of-age-related-macular-degeneration
#6
Stephen Burgess, George Davey Smith
PURPOSE: Undertake a systematic investigation into associations between genetic predictors of lipid fractions and age-related macular degeneration (AMD) risk. DESIGN: Two-sample Mendelian randomization investigation using published data. PARTICIPANTS: A total of 33 526 individuals (16 144 cases, 17 832 controls) predominantly of European ancestry from the International Age-related Macular Degeneration Genomics Consortium. METHODS: We consider 185 variants previously demonstrated to be associated with at least 1 of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, or triglycerides at a genome-wide level of significance, and test their associations with AMD...
April 26, 2017: Ophthalmology
https://www.readbyqxmd.com/read/28447802/potential-lipid-lowering-mechanisms-of-biochanin-a
#7
Zhaohui Xue, Qian Zhang, Wancong Yu, Haichao Wen, Xiaonan Hou, Dan Li, Xiaohong Kou
Extensive studies have demonstrated that biochanin A (BCA) has a significant hypolipidemic effect. However, its mechanism of action is not clear. In this context, the effect of BCA on a high-fat diet (HFD)-induced hyperlipidemia in mice was determined. The results showed that treatment with a medium dose of biochanin A (BM) significantly decreased low-density lipoprotein cholesterol (LDL-C) 85% (from 1.196 ± 0.183 to 0.181 ± 0.0778 mM) and total cholesterol (TC) 39% (from 5.983 ± 0.128 to 3.649 ± 0.374 mM) levels, increased lipoprotein lipase (LPL) 96% (from 1...
May 4, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28432183/anacetrapib-driven-triglyceride-lowering-explained-the-fortuitous-role-of-cetp-in-the-intravascular-catabolism-of-triglyceride-rich-lipoproteins
#8
Amanda L Brown, J Mark Brown
No abstract text is available yet for this article.
April 21, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28428701/association-of-cholesteryl-ester-transfer-protein-cetp-gene-629c-a-polymorphism-with-angiographically-proven-atherosclerosis
#9
Anita Devi, Ritu Singh, Rajni Dawar, Sanjay Tyagi
Association of cholesteryl ester transfer protein (CETP) Gene -629C/A Polymorphism with angiographically proven atherosclerosis CETP gene has been linked to CAD risk via its role in HDL and LDL metabolism. There is no agreement of whether CETP is atherogenic or not. Furthermore, various genotypes of CETP gene have been associated with CETP levels and thus with atherosclerosis risk. Our aim was to study the association of CETP -629C/A gene polymorphism with CETP and HDL levels and their association if any with atherosclerosis...
June 2017: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/28428219/deficiency-of-cholesteryl-ester-transfer-protein-protects-against-atherosclerosis-in-rabbits
#10
Jifeng Zhang, Manabu Niimi, Dongshan Yang, Jingyan Liang, Jie Xu, Tokuhide Kimura, Anna V Mattew, Yanhong Guo, Yanbo Fan, Tianqing Zhu, Jun Song, Rose Ackermann, Yui Koike, Anna Schwendeman, Liangxue Lai, Subramaniam Pennathur, Minerva Garcia-Barrio, Jianglin Fan, Y Eugene Chen
OBJECTIVE: CETP (cholesteryl ester transfer protein) plays an important role in lipoprotein metabolism; however, whether inhibition of CETP activity can prevent cardiovascular disease remains controversial. APPROACH AND RESULTS: We generated CETP knockout (KO) rabbits by zinc finger nuclease gene editing and compared their susceptibility to cholesterol diet-induced atherosclerosis to that of wild-type (WT) rabbits. On a chow diet, KO rabbits showed higher plasma levels of high-density lipoprotein (HDL) cholesterol than WT controls, and HDL particles of KO rabbits were essentially rich in apolipoprotein AI and apolipoprotein E contents...
April 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28425253/association-of-the-cetp-gene-taqib-and-d442g-polymorphisms-with-essential-hypertension-in-the-chinese-mongolian-population
#11
Shudong Niu, Xiaoming Tao, Jingping Li, Yongyue Liu, Jian Wang, Mingyu Cong, Keyong Zhang, Wenyu Zhou, Changchun Qiu
BACKGROUND/AIM: This study aimed to explore the associations of the cholesteryl ester transfer protein (CETP) gene TaqIB and D442G polymorphisms with essential hypertension (EH). MATERIALS AND METHODS: In this case-control study, 883 hypertensive patients and 1044 normal controls were randomly selected from the Mongolian population of China. Polymerase chain reaction (PCR) and direct sequencing of PCR products were used to identify the genotypes. Haplotype analysis was performed by estimating the haplotype frequencies using the online SHEsis package...
April 18, 2017: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/28422089/thermogenic-adipocytes-promote-hdl-turnover-and-reverse-cholesterol-transport
#12
Alexander Bartelt, Clara John, Nicola Schaltenberg, Jimmy F P Berbée, Anna Worthmann, M Lisa Cherradi, Christian Schlein, Julia Piepenburg, Mariëtte R Boon, Franz Rinninger, Markus Heine, Klaus Toedter, Andreas Niemeier, Stefan K Nilsson, Markus Fischer, Sander L Wijers, Wouter van Marken Lichtenbelt, Ludger Scheja, Patrick C N Rensen, Joerg Heeren
Brown and beige adipocytes combust nutrients for thermogenesis and through their metabolic activity decrease pro-atherogenic remnant lipoproteins in hyperlipidemic mice. However, whether the activation of thermogenic adipocytes affects the metabolism and anti-atherogenic properties of high-density lipoproteins (HDL) is unknown. Here, we report a reduction in atherosclerosis in response to pharmacological stimulation of thermogenesis linked to increased HDL levels in APOE*3-Leiden.CETP mice. Both cold-induced and pharmacological thermogenic activation enhances HDL remodelling, which is associated with specific lipidomic changes in mouse and human HDL...
April 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28412650/comparative-effects-of-cholesteryl-ester-transfer-protein-inhibition-statin-or-ezetimibe-on-lipid-factors-the-accentuate-trial
#13
Stephen J Nicholls, Kausik K Ray, Christie M Ballantyne, Lauren A Beacham, Debra L Miller, Giacomo Ruotolo, Steven E Nissen, Jeffrey S Riesmeyer
BACKGROUND AND AIMS: The optimal approaches to management of patients treated with moderate statin doses on lipid parameters are unknown. The ACCENTUATE study aimed to compare the effects of adding the cholesteryl ester transfer protein inhibitor (CETP) evacetrapib, ezetimibe or increasing statin dose in atorvastatin-treated high-vascular risk patients on lipid parameters. METHODS: 366 patients with atherosclerotic cardiovascular disease (ASCVD) and/or diabetes were treated with atorvastatin 40 mg/day for 28 days prior to randomization to atorvastatin 40 mg plus evacetrapib 130 mg, atorvastatin 80 mg, atorvastatin 40 mg plus ezetimibe 10 mg or atorvastatin 40 mg plus placebo, daily for 90 days at 64 centers in the United States...
April 8, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28408313/preventing-cardiovascular-heart-disease-promising-nutraceutical-and-non-nutraceutical-treatments-for-cholesterol-management
#14
REVIEW
T P Johnston, T A Korolenko, M Pirro, A Sahebkar
Hypercholesterolemia is one of the major risk factors for the development of cardiovascular disease. Atherosclerosis resulting from hypercholesterolemia causes many serious cardiovascular diseases. Statins are generally accepted as a treatment of choice for lowering low-density lipoprotein (LDL) cholesterol, which reduces coronary heart disease morbidity and mortality. Since statin use can be associated with muscle problems and other adverse symptoms, non-adherence and discontinuation of statin therapy often leads to inadequate control of plasma cholesterol levels and increased cardiovascular risk...
June 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28398632/prenatal-and-postnatal-assessment-in-rabbits-with-evacetrapib-a-cholesteryl-ester-transfer-protein-inhibitor
#15
William J Breslin, Kim G Hilbish, Ellen A Cannady, Tammy L Edwards
BACKGROUND: Evacetrapib, a potent and selective inhibitor of cholesteryl ester transfer protein (CETP), was under development for the treatment of cardiovascular (CV) disease. The purpose of this pre-postnatal study in rabbits was to evaluate the effects of evacetrapib on pregnancy, parturition, and lactation of the maternal animals and on the growth, viability, development, and reproductive performance of the first filial (F1) offspring. The rabbit is considered a relevant species for toxicity testing with evacetrapib as it demonstrates significant CETP expression, whereas mice and rats do not express significant levels of CETP...
April 17, 2017: Birth Defects Res
https://www.readbyqxmd.com/read/28398618/fertility-and-embryo-fetal-development-assessment-in-rats-and-rabbits-with-evacetrapib-a-cholesteryl-ester-transfer-protein-inhibitor
#16
William J Breslin, Kim G Hilbish, Ellen A Cannady, Tammy L Edwards
BACKGROUND: The purpose of these studies was to evaluate the effects of evacetrapib on male and female fertility and on embryo-fetal development (EFD). METHODS: Evacetrapib, a potent and selective inhibitor of cholesteryl ester transfer protein (CETP), was administered daily by oral gavage starting 2 weeks (for female) or 4 weeks (for male) before mating, during cohabitation, and until necropsy in the male rat fertility study or through gestation day (GD) 17 in the female rat combined fertility/EFD study...
April 17, 2017: Birth Defects Res
https://www.readbyqxmd.com/read/28395380/streptozotocin-treated-high-fat-fed-mice-a-new-type-2-diabetes-model-used-to-study-canagliflozin-induced-alterations-in-lipids-and-lipoproteins
#17
Tian Yu, Mitchell J Sungelo, Ira J Goldberg, Hong Wang, Robert H Eckel
The pharmacological effects of type 2 diabetes (T2DM) medications on lipoprotein metabolism are difficult to assess in preclinical models because those created failure to replicate the human condition in which insulin deficiency is superimposed on obesity-related insulin resistance. To create a better model, we fed mice with high fat (HF) diet and treated the animals with low dose streptozotocin (STZ) to mimic T2DM. We used this model to evaluate the effects of canagliflozin (CANA), a drug that reduces plasma glucose by inhibiting the sodium-glucose transporter 2 (SGLT2), which mediates ~90% of renal glucose reabsorption] on lipid and lipoprotein metabolism...
May 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28387842/association-of-cholesterol-ester-transfer-protein-taq-ib-polymorphism-with-acute-coronary-syndrome-in-egyptian-national-patients
#18
Sahar M Abdel Maksoud, Wael T El-Garf, Ola S Ali, Gamal M Shaaban, Noha N Amer
Background: The association between cholesterol ester transfer protein (CETP) Taq IB polymorphism and coronary artery disease (CAD) has been studied in different populations. Acute coronary syndrome (ACS) is a group of clinical symptoms within acute myocardial ischemia, including unstable angina (UA) and myocardial infarction (MI). Because there are no data reported in the literature concerning the cholesteryl ester transfer protein (CETP) Taq IB polymorphism in Egyptians, our study aimed to investigate the frequency of different CETP Taq IB genotypes in Egyptian patients with ACS and in healthy control individuals...
May 1, 2017: Laboratory Medicine
https://www.readbyqxmd.com/read/28380664/chronic-administration-of-anacetrapib-is-associated-with-accumulation-in-adipose-and-slow-elimination
#19
R Krishna, F Gheyas, Y Liu, D R Hagen, B Walker, A Chawla, J Cote, R O Blaustein, D E Gutstein
Anacetrapib is a novel cholesteryl-ester transfer protein (CETP) inhibitor in late-stage clinical development, shown in preceding clinical trials to have residual pharmacological activity after prolonged washout after chronic dosing. Preclinical findings suggest that white adipose tissue is a potential depot and that accumulation into adipose tissue governs the long-term kinetics of anacetrapib in mice. A phase I study performed to test this hypothesis in humans revealed that plasma exposure was correlated with fat content in food administered with the drug...
April 5, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28378447/a-genome-wide-linkage-and-association-analysis-of-imputed-insertions-and-deletions-with-cardiometabolic-phenotypes-in-mexican-americans-the-insulin-resistance-atherosclerosis-family-study
#20
Chuan Gao, Fang-Chi Hsu, Latchezar M Dimitrov, Hayrettin Okut, Yii-Der I Chen, Kent D Taylor, Jerome I Rotter, Carl D Langefeld, Donald W Bowden, Nicholette D Palmer
Insertions and deletions (INDELs) represent a significant fraction of interindividual variation in the human genome yet their contribution to phenotypes is poorly understood. To confirm the quality of imputed INDELs and investigate their roles in mediating cardiometabolic phenotypes, genome-wide association and linkage analyses were performed for 15 phenotypes with 1,273,952 imputed INDELs in 1,024 Mexican-origin Americans. Imputation quality was validated using whole exome sequencing with an average kappa of 0...
April 5, 2017: Genetic Epidemiology
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