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Lisa R Hoving, Saeed Katiraei, Marieke Heijink, Amanda Pronk, Lianne van der Wee-Pals, Trea Streefland, Martin Giera, Ko Willems van Dijk, Vanessa van Harmelen
SCOPE: Mannan oligosaccharides (MOS) have proven effective at improving growth performance, while also reducing hyperlipidemia and inflammation. As atherosclerosis is accelerated both by hyperlipidemia and inflammation, we aimed to determine the effect of dietary MOS on atherosclerosis development in hyperlipidemic ApoE*3-Leiden.CETP (E3L.CETP) mice, a well-established model for human-like lipoprotein metabolism. METHODS AND RESULTS: Female E3L.CETP mice were fed a high cholesterol diet, with or without 1% MOS for 14 weeks...
April 17, 2018: Molecular Nutrition & Food Research
Philip J Barter, Kerry-Anne Rye
Cholesteryl ester transfer protein (CETP) promotes the transfer of cholesteryl esters from the nonatherogenic high density lipoprotein (HDL) fraction to potentially proatherogenic non-HDL fractions. Inhibition of CETP reduces the concentration of non-HDL cholesterol, enhances HDL functionality, and increases the concentration of HDL cholesterol and apoA-I. Despite an absence of benefit in earlier trials of CETP inhibition, the REVEAL trial has shown that treatment with the CETP inhibitor anacetrapib reduces the risk of having a coronary event in high-risk, statin-treated patients...
May 2018: Cardiology Clinics
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No abstract text is available yet for this article.
March 2018: Physiological Reports
Prasanna Diddige Revanasiddappa, Revathi Sankar, Sanjib Senapati
Cholesteryl Ester Transfer Protein (CETP) facilitates the transfer of cholesteryl esters (CEs) from antiatherogenic HDLs to proatherogenic LDLs. Inhibition of CETP is therefore being pursued as a potential strategy to reduce cardiovascular risk. Crystal structure of CETP has revealed the existence of two neutral CEs and two charged phospholipids (PLs) in its hydrophobic tunnel. This is in direct contrast to the other lipid binding proteins that contain only two bound lipids. Moreover, previous animal studies on mice showed no detectable phospholipid transfer activity of CETP...
March 28, 2018: Journal of Physical Chemistry. B
M John Chapman, Alexina Orsoni, Paul Robillard, Patrice Therond, Philippe Giral
BACKGROUND: Statins impact the metabolism, concentrations, composition, and function of circulating lipoproteins. OBJECTIVE: We evaluated time course relationships between statin-mediated reduction in atherogenic apolipoprotein B (ApoB)-containing particles and dynamic intravascular remodeling of ApoAI-containing lipoprotein subpopulations in the mixed dyslipidemia of metabolic syndrome. METHODS: Insulin-resistant, hypertriglyceridemic, hypercholesterolemic, obese males (n = 12) were treated with pitavastatin (4 mg/d) and response evaluated at 6, 42, and 180 days...
February 9, 2018: Journal of Clinical Lipidology
Gilberto Vargas-Alarcon, Oscar Perez-Mendez, Gabriel Herrera-Maya, Cynthia Garcia-Sanchez, Marco Antonio Martinez-Rios, Marco Antonio Peña-Duque, Rosalinda Posadas-Sanchez, Carlos Posadas-Romero, Galileo Escobedo, Jose Manuel Fragoso
We evaluated whether CETP and LCAT gene polymorphisms are statistically associated with the high-density lipoprotein (HDL) size distribution, the cholesterol level of HDL subclasses, and the acute coronary syndrome (ACS) susceptibility. Two CETP gene polymorphisms (rs4783961 and rs708272) and one LCAT polymorphism (rs2292318) were genotyped by 5' exonuclease TaqMan assays in 619 patients with ACS and 607 control individuals. For HDL analysis, a subgroup of 100 healthy individuals was recruited; the HDL subclasses were separated via ultracentrifugation and polyacrylamide gradient gel electrophoresis under native conditions...
March 23, 2018: Lipids
Zbyszko Chowaniec, Anna Skoczyńska
Cardiovascular diseases are still the main cause of death in Poland and throughout the world. Independent risk factors of cardiovascular disease, in addition to elevated LDL cholesterol, are both low HDL levels and high levels of non-HDL cholesterol. Plasma phospholipid-transfer protein (PLTP) and cholesteryl ester transfer protein (CETP) both play a major role in the metabolism of those lipoproteins. A lack of these proteins increases HDL and lowers LDL levels. In the light of current knowledge, it seems reasonable to search for compounds that may decrease the activity of CETP, and thus reduce the incidence of cardiovascular disease...
March 16, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Parisa Naseri, Soheila Khodakarim, Kamran Guity, Maryam S Daneshpour
BACKGROUND: Mechanisms of metabolic syndrome (MetS) causation are complex, genetic and environmental factors are important factors for the pathogenesis of MetS In this study, we aimed to evaluate familial and genetic influences on metabolic syndrome risk factor and also assess association between FTO (rs1558902 and rs7202116) and CETP(rs1864163) genes' single nucleotide polymorphisms (SNP) with low HDL_C in the Tehran Lipid and Glucose Study (TLGS). MATERIALS AND METHODS: The design was a cross-sectional study of 1776 members of 227 randomly-ascertained families...
March 14, 2018: Gene
Zhao Dong, Haozhe Shi, Mingming Zhao, Xin Zhang, Wei Huang, Yuhui Wang, Lemin Zheng, Xunde Xian, George Liu
OBJECTIVE: Lecithin cholesterol acyltransferase (LCAT) plays a pivotal role in HDL metabolism but its influence on atherosclerosis remains controversial for decades both in animal and clinical studies. Because lack of cholesteryl ester transfer protein (CETP) is a major difference between murine and humans in lipoprotein metabolism, we aimed to create a novel Syrian Golden hamster model deficient in LCAT activity, which expresses endogenous CETP, to explore its metabolic features and particularly the influence of LCAT on the development of atherosclerosis...
March 8, 2018: Metabolism: Clinical and Experimental
Bahareh Sedaghati-Khayat, Maryam Barzin, Mahdi Akbarzadeh, Kamran Guity, Mohammad-Sadegh Fallah, Hoda Pourhassan, Fereidoun Azizi, Maryam S Daneshpour
BACKGROUND: Obesity is currently an international epidemic and metabolic derangements pose these individuals at greater risk for future morbidity and mortality. Genetics and environmental factors have undeniable effects and among genetic risk factors, FTO/CETP genes are important. The current study examines the interaction between obesity phenotypes and FTO/CETP SNPs and their effects on lipid profile changes. MATERIALS AND METHODS: We selected 954 adult subjects from TCGS (47...
March 10, 2018: Eating and Weight Disorders: EWD
Sam J L van der Tuin, Zhuang Li, Jimmy F P Berbée, Inge Verkouter, Linda E Ringnalda, Annette E Neele, Jan B van Klinken, Sander S Rensen, Jingyuan Fu, Menno P J de Winther, Albert K Groen, Patrick C N Rensen, Ko Willems van Dijk, Yanan Wang
BACKGROUND: Lipopolysaccharide (LPS) decreases hepatic CETP (cholesteryl ester transfer protein) expression albeit that the underlying mechanism is disputed. We recently showed that plasma CETP is mainly derived from Kupffer cells (KCs). In this study, we investigated the role of KC subsets in the mechanism by which LPS reduces CETP expression. METHODS AND RESULTS: In CETP-transgenic mice, LPS markedly decreased hepatic CETP expression and plasma CETP concentration without affecting hepatic macrophage number...
March 10, 2018: Journal of the American Heart Association
W Masson, M Lobo, D Siniawski, M Huerín, G Molinero, R Valéro, J P Nogueira
BACKGROUND: Cholesteryl ester transfer protein (CETP) inhibitors are a class of drugs that targets the CETP enzyme to significantly increase serum high-density lipoprotein cholesterol (HDL-C) and decrease low-density lipoprotein cholesterol (LDL-C) levels. As HDL-C has potential antidiabetic properties, and the beneficial effects of CETP drugs on glucose homoeostasis have not been sufficiently studied, the aims of this study were: (1) to evaluate the effect of CETP inhibitors on the incidence of diabetes; and (2) to assess the association between CETP inhibitor-induced changes in HDL-C levels and incidence of diabetes...
February 20, 2018: Diabetes & Metabolism
Sheila A Doggrell
The actions of the cholesteryl ester transfer protein (CETP) inhibitors (torcetrapib, dalcetrapib and evacetrapib) include increasing high-density lipoprotein (HDL) cholesterol, but they do not reduce cardiovascular outcomes in subjects with high cardiovascular risk. Anacetrapib also inhibits CETP, increases HDL cholesterol and lowers low-density lipoprotein (LDL) cholesterol. Areas covered: This evaluation is of the REVEAL (Randomized Evaluation of the Effects of Anacetrapib through Lipid Modification) trial, which was a cardiovascular outcomes trial with anacetrapib in subjects with high cardiovascular risk...
March 12, 2018: Expert Opinion on Pharmacotherapy
Sudichhya Shrestha, Ben J Wu, Liam Guiney, Philip J Barter, Kerry-Anne Rye
Most of the cholesterol in plasma is in an esterified form that is generated in potentially cardioprotective high density lipoproteins (HDLs). Cholesteryl ester transfer protein (CETP) mediates bidirectional transfers of cholesteryl esters (CE) and triglycerides (TG) between plasma lipoproteins. Since CE originates in HDLs, and TG enters the plasma as a component of very low density lipoproteins (VLDLs), activity of CETP results in a net mass transfer of CE from HDLs to VLDLs and low density lipoproteins (LDLs), and of TG from VLDLs to LDLs and HDLs...
February 27, 2018: Journal of Lipid Research
Yusuke Masuda, Shinji Yamaguchi, Chikako Suzuki, Takahide Aburatani, Yuki Nagano, Ryuki Miyauchi, Eiko Suzuki, Naotoshi Yamamura, Kentaro Nagatomo, Hidetoshi Ishihara, Kazuaki Okuno, Futoshi Nara, Gabriele Matschiner, Ryuji Hashimoto, Tohru Takahashi, Tomohiro Nishizawa
Since it was recently reported that an antibody for proprotein convertase subtilisin/kexin type 9 (PCSK9) reduced the risk of cardiovascular events in a clinical context, PCSK9 inhibition is thought to be an attractive therapy for dyslipidemia. In the present study, we created a novel small biologic alternative to PCSK9 antibodies called DS-9001a, comprising an albumin binding domain fused to an artificial lipocalin mutein (ABD-fused Anticalin protein), which can be produced by a microbial production system...
February 20, 2018: Journal of Pharmacology and Experimental Therapeutics
Ashwini V Padalkar, Rakesh Kumar
This study investigated the occurrence, removal and influence of plant-operating conditions on removal mechanisms of 83 VOCs in different treatment units of a CETP in Mumbai, treating industrial waste on primary and secondary level. A mass balance approach was used to predict VOC removal by volatilization, stripping, weir drop, adsorption, and biodegradation. Results indicate that ∼17% of VOCs were removed by stripping in equalization tank and ∼8% were removed by weir drop in primary clari-flocculator respectively...
February 1, 2018: Chemosphere
Zhaohui Xue, Xiaonan Hou, Wancong Yu, Haichao Wen, Qian Zhang, Dan Li, Xiaohong Kou
The effects of CPe-III on hyperlipidemic mice were investigated, along with molecular docking and dynamics analyses between CPe-III and CETP. This study was conducted in order to explore the lipid metabolism potential and mechanism of CPe-III. CPe-III significantly (P<0.05) reduced serum total cholesterol, triglyceride and hepatic triglyceride levels and increased serum superoxide dismutase activity. CPe-III reversed liver changes induced by a high-fat diet and significantly (P<0.05) reduced kidney and epididymal fat indices...
February 2018: Food Research International
Xinran Wang, Wei Li, Lijuan Hao, Honglei Xie, Chenzhou Hao, Chunchi Liu, Wenyan Li, Xuqiong Xiong, Dongmei Zhao
Epidemiological studies have identified that high levels of low-density lipoprotein-cholesterol (LDL-C) and low levels of high-density lipoprotein-cholesterol (HDL-C) are two independent causes of cardiovascular disease (CVD). Statins, niacin and fibrate are used for the treatment of CVD. However, some defects are shown in the treatment process. Thus, there is a demand for better treatment strategies that confer preferable efficacy with fewer side effects. Cholesteryl ester transfer protein (CETP) promotes the movement of CEs from HDL to LDL and VLDL in exchange for triglycerides (TGs)...
February 9, 2018: Expert Opinion on Therapeutic Patents
Angela Andaleon, Lauren S Mogil, Heather E Wheeler
Plasma lipid levels are risk factors for cardiovascular disease, a leading cause of death worldwide. While many studies have been conducted on lipid genetics, they mainly focus on Europeans and thus their transferability to diverse populations is unclear. We performed SNP- and gene-level genome-wide association studies (GWAS) of four lipid traits in cohorts from Nigeria and the Philippines and compared them to the results of larger, predominantly European meta-analyses. Two previously implicated loci met genome-wide significance in our SNP-level GWAS in the Nigerian cohort, rs34065661 in CETP associated with HDL cholesterol (P = 9...
2018: PeerJ
C M Schooling, J V Huang, J V Zhao, M K Kwok, S L Au Yeung, S L Lin
BACKGROUND: Development of pharmacological treatments to mitigate ischemic heart disease (IHD) has encompassed disappointing results and expensive failures, which has discouraged investment in new approaches to prevention and control. New treatments are most likely to be successful if they act on genetically validated targets. We assessed whether existing pharmacological treatments for IHD reduction are acting on genetically validated targets and whether all such targets for IHD are currently being exploited...
January 30, 2018: EBioMedicine
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