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https://www.readbyqxmd.com/read/29907965/the-genetic-architecture-of-diet-induced-hepatic-fibrosis-in-mice
#1
Simon T Hui, Zeyneb Kurt, Iina Tuominen, Frode Norheim, Richard C Davis, Calvin Pan, Darwin L Dirks, Clara E Magyar, Samuel W French, Karthickeyan Chella Krishnan, Simon Sabir, Francisco Campos-Pérez, Nahum Méndez-Sánchez, Luis Macías-Kauffer, Paola León-Mimila, Samuel Canizales-Quinteros, Xia Yang, Simon W Beaven, Adriana Huertas-Vazquez, Aldons J Lusis
We report the genetic analysis of a "humanized" hyperlipidemic mouse model for progressive nonalcoholic steatohepatitis (NASH) and fibrosis. Mice carrying transgenes for human APOE*3-Leiden and CETP and fed a "Western" diet were studied on the genetic backgrounds of over 100 inbred mouse strains. The mice developed hepatic inflammation and fibrosis that was highly dependent on genetic background, with vast differences in the degree of fibrosis. Histological analysis showed features characteristic of human NASH, including macrovesicular steatosis, hepatocellular ballooning, inflammatory foci and pericellular collagen deposition...
June 16, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29902703/metabolic-liver-inflammation-in-obesity-does-not-robustly-decrease-hepatic-and-circulating-cetp
#2
Lisanne L Blauw, Zhuang Li, Sander S Rensen, Jan Willem M Greve, Aswin Verhoeven, Rico J Derks, Martin Giera, Yanan Wang, Patrick C N Rensen
BACKGROUND AND AIMS: We recently showed that plasma cholesteryl ester transfer protein (CETP) is mainly derived from VSIG4-positive Kupffer cells. Activation of these cells by the bacterial endotoxin lipopolysaccharide (LPS) strongly decreases CETP expression. As Kupffer cell activation plays a detrimental role in the progression of non-alcoholic fatty liver disease (NAFLD), we aimed to study if metabolic liver inflammation is also associated with a decrease in hepatic and circulating CETP...
June 7, 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29901215/cetp-inhibition-and-hdl-cholesterol-a-story-of-cv-risk-or-cv-benefit-or-both
#3
REVIEW
Stephen J Nicholls
No abstract text is available yet for this article.
June 14, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29883800/structural-basis-of-the-lipid-transfer-mechanism-of-phospholipid-transfer-protein-pltp
#4
Meng Zhang, Xiaobo Zhai, Jinping Li, John J Albers, Simona Vuletic, Gang Ren
Human phospholipid transfer protein (PLTP) mediates the transfer of phospholipids among atheroprotective high-density lipoproteins (HDL) and atherogenic low-density lipoproteins (LDL) by an unknown mechanism. Delineating this mechanism would represent the first step towards understanding PLTP-mediated lipid transfers, which may be important for treating lipoprotein abnormalities and cardiovascular disease. Here, using various electron microscopy techniques, PLTP is revealed to have a banana-shaped structure similar to cholesteryl ester transfer protein (CETP)...
June 5, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29879115/in-vivo-and-in-silico-dynamics-of-the-development-of-metabolic-syndrome
#5
Yvonne J W Rozendaal, Yanan Wang, Yared Paalvast, Lauren L Tambyrajah, Zhuang Li, Ko Willems van Dijk, Patrick C N Rensen, Jan A Kuivenhoven, Albert K Groen, Peter A J Hilbers, Natal A W van Riel
The Metabolic Syndrome (MetS) is a complex, multifactorial disorder that develops slowly over time presenting itself with large differences among MetS patients. We applied a systems biology approach to describe and predict the onset and progressive development of MetS, in a study that combined in vivo and in silico models. A new data-driven, physiological model (MINGLeD: Model INtegrating Glucose and Lipid Dynamics) was developed, describing glucose, lipid and cholesterol metabolism. Since classic kinetic models cannot describe slowly progressing disorders, a simulation method (ADAPT) was used to describe longitudinal dynamics and to predict metabolic concentrations and fluxes...
June 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29867549/exercise-training-favorably-modulates-gene-and-protein-expression-that-regulate-arterial-cholesterol-content-in-cetp-transgenic-mice
#6
Paula R Pinto, Karolline S da Silva, Rodrigo T Iborra, Ligia S Okuda, Diego Gomes-Kjerulf, Guilherme S Ferreira, Adriana Machado-Lima, Debora D F M Rocco, Edna R Nakandakare, Ubiratan F Machado, Maria L Correa-Giannella, Sergio Catanozi, Marisa Passarelli
Aerobic exercise training (AET) improves the reverse cholesterol transport (RCT) in cholesteryl ester transfer protein-transgenic (CETP-tg) mice. We aimed at investigating the role of AET in the expression of genes and proteins involved in lipid flux in the aorta and macrophages of CETP-tg mice. Three-month-old male mice were randomly divided into trained (T; treadmill 15 m/min; 30 min/day) and sedentary (S) groups. After 6 weeks, peritoneal macrophages and the aortic arch were obtained immediately (0 h) or 48 h after the last exercise session...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29848931/study-of-the-association-of-17-lipid-related-gene-polymorphisms-with-coronary-heart-disease
#7
Nan Wu, Guili Liu, Yi Huang, Qi Liao, Liyuan Han, Huandan Ye, Shiwei Duan, Xiaomin Chen
OBJECTIVE: Blood lipids are well-known risk factors for coronary heart disease (CHD). The aim of this study was to explore the association between 17 lipid-related gene polymorphisms and CHD. METHODS: The current study examined with 784 CHD cases and 739 non-CHD controls. Genotyping was performed on the MassARRAY iPLEX® assay platform. RESULTS: Our analyses revealed a significant association of APOE rs7259620 with CHD (genotype: χ2=6.353, df=2, p=0...
June 2018: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/29800275/from-lipid-locus-to-drug-target-through-human-genomics
#8
Sander W van der Laan, Eric L Harshfield, Daiane Hemerich, David Stacey, Angela M Wood, Folkert W Asselbergs
In the last decade over 175 genetic loci have robustly been associated to levels of major circulating blood lipids. Most loci are specific to one or two lipids, while some (SUGP1, ZPR1, TRIB1, HERPUD1, and FADS1) are associated to all. While exposing the polygenic architecture of circulating lipids and the underpinnings of dyslipidemia, these genome-wide association studies (GWAS) have provided further evidence of the critical role that lipids play in coronary heart disease (CHD) risk, as indicated by the 2...
May 23, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29783755/a-miniaturized-extruder-to-prototype-amorphous-solid-dispersions-selection-of-plasticizers-for-hot-melt-extrusion
#9
Matthias E Lauer, Reto Maurer, Anne T De Paepe, Cordula Stillhart, Laurence Jacob, Rajesh James, Yuki Kojima, Rene Rietmann, Tom Kissling, Joost A van den Ende, Sabine Schwarz, Olaf Grassmann, Susanne Page
Hot-melt extrusion is an option to fabricate amorphous solid dispersions and to enhance oral bioavailability of poorly soluble compounds. The selection of suitable polymer carriers and processing aids determines the dissolution, homogeneity and stability performance of this solid dosage form. A miniaturized extrusion device (MinEx) was developed and Hypromellose acetate succinate type L (HPMCAS-L) based extrudates containing the model drugs neurokinin-1 (NK1) and cholesterylester transfer protein (CETP) were manufactured, plasticizers were added and their impact on dissolution and solid-state properties were assessed...
May 19, 2018: Pharmaceutics
https://www.readbyqxmd.com/read/29772998/partially-purified-aqueous-fraction-of-desmodium-gyrans-dc-improves-reverse-cholesterol-transport-and-lipoprotein-metabolism-in-wistar-rats-fed-with-high-fat-diet
#10
M S Indu, Jose Padikkala, Achuthan C Raghavamenon
Apart from the conventional hypolipidemic therapy, plaque regression through enhanced reverse cholesterol transport (RCT) has emerged as novel approach in atherosclerotic drug development. High-density lipoprotein (HDL) mimetics as well as agents that augment the functional HDL and RCT pathways are under intense exploration. Desmodium gyrans (Fabacea) has been shown to have hypolipidemic efficacy, with an HDL-enhancing property. In this study, a chromatographically purified active fraction of D. gyrans (DGMAF) significantly decreased the serum and lipid profiles as well as lipotoxicity in liver in Wistar rats fed with high-fat diet (HFD)...
2018: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/29766560/further-options-for-treating-lipids-in-people-with-diabetes-targeting-ldl-cholesterol-and-beyond
#11
REVIEW
A S Wierzbicki
Diabetes is associated with increased cardiovascular disease (CVD) risk. Previous studies with statins have established that a 1 mmol/l reduction in LDL-cholesterol reduces CVD events by 21% over 5 years in people with diabetes. More recently, trials in people with acute coronary syndromes showed that ezetimibe reduced CVD events by 6% at 5 years and achieved a LDL-cholesterol of 1.6 mmol/l with better results in people with Type 2 diabetes. Several novel lipid-lowering therapies have recently been developed...
May 15, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/29751583/blood-pressure-lowering-effect-of-cuban-policosanol-is-accompanied-by-improvement-of-hepatic-inflammation-lipoprotein-profile-and-hdl-quality-in-spontaneously-hypertensive-rats
#12
Kyung-Hyun Cho, Dhananjay Yadav, Suk-Jeong Kim, Jae-Ryong Kim
We investigated the antihypertensive effect of policosanol on spontaneously hypertensive rats (SHR). For this, we analyzed blood pressure, blood lipid, and lipoprotein properties in male SHR after consumption of Cuban policosanol (PCO). The experimental groups were as follows: normotensive Wistar Kyoto (WKY) control, SHR group fed normal diet (ND), SHR group fed 20 mg of PCO, SHR group fed 100 mg of PCO, and SHR group fed 200 mg of PCO per kg of body weight. After eight weeks, the SHR control group showed gradual increases up to 21% in systolic blood pressure (SBP) and diastolic blood pressure (DBP) compared with values at week 0...
May 3, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29747087/hdl-cholesterol-efflux-capacity-and-cholesteryl-ester-transfer-are-associated-with-body-mass-but-are-not-changed-by-diet-induced-weight-loss-a-randomized-trial-in-abdominally-obese-men
#13
Charlotte P J Talbot, Jogchum Plat, Peter J Joris, Maurice Konings, Yvo H A M Kusters, Casper G Schalkwijk, Andreas Ritsch, Ronald P Mensink
BACKGROUND AND AIMS: Obesity is associated with a lower HDL-mediated cholesterol efflux from macrophages and a higher CETP (cholesteryl ester transfer protein) activity, but effects of weight loss are not clear. In addition, associations with visceral and subcutaneous adipose tissue are not known. We therefore investigated effects of diet-induced weight loss on HDL-mediated cholesterol efflux and cholesterol ester (CE) transfer in abdominally obese men. Differences between normal-weight and abdominally obese men were also examined...
April 28, 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29740798/new-insight-on-a-combination-of-policosanol-and-10-dehydrogingerdione-phytochemicals-as-inhibitors-for-platelet-activation-biomarkers-and-atherogenicity-risk-in-dyslipidemic-rabbits-role-of-cetp-and-pcsk9-inhibition
#14
Mohamed Mahmoud Elseweidy, Rawia Sarhan Amin, Hebatallah Husseini Atteia, Reham Raafat El-Zeiky, Naif A Al-Gabri
Platelet markers [soluble p selectin (sP-selectin) and soluble CD40 ligand (sCD40L)] are associated with platelet activation and cardiovascular risk. Both policosanol and 10-dehydrogingerdione are natural products with proven CETP inhibitory and antiatherogenic effects. Present work aimed mainly to investigate the levels of platelet activation biomarkers in the serum of dyslipidemic rabbits and the potential of these phytochemicals either alone or in a combination form to protect against atherogenicity. Additionally, this work clarified their effect on PCSK9, a key player in atherosclerosis progression...
May 9, 2018: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/29736804/influence-of-fatty-acid-modification-on-uptake-of-lovastatin-loaded-reconstituted-high-density-lipoprotein-by-foam-cells
#15
Yun Yang, Ji Wang, Hongliang He, Wenli Zhang, Yuansheng Zhang, Jianping Liu
PURPOSE: Spherical reconstituted high density lipoprotein (rHDL) can target atherosclerotic lesions by the very low density lipoprotein (VLDL) receptor, which is seldom expressed in liver. By promoting this pathway, the targeting efficiency was hyphothesized to be improved due to avoiding undesired uptake in liver mediated by the scavenger receptor class B type I (SR-BI). In this study, how fatty acid modification in spherical rHDL influenced the VLDL receptor-mediated endocytosis pathway was investigated...
May 7, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29730761/clinical-pharmacokinetics-and-pharmacodynamics-of-dalcetrapib
#16
REVIEW
Donald M Black, Darren Bentley, Sunny Chapel, Jongtae Lee, Emily Briggs, Therese Heinonen
The cholesterol ester transfer protein (CETP) inhibitor dalcetrapib has been under evaluation for its potential to prevent cardiovascular (CV) events for almost two decades. The current clinical development program, representing new advances in precision medicine and focused on a genetically defined population with acute coronary syndrome (ACS), is supported by a large body of pharmacokinetic and pharmacodynamic data as well as substantial clinical experience in over 13,000 patients and volunteers. Dalcetrapib treatment of 600 mg/day produces significant inhibition of CETP activity, and has been utilized in phase II and III studies, including CV endpoint trials...
May 5, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29728915/results-meta-analysis-and-a-first-evaluation-of-u-nox-r-the-urinary-nitrate-to-nitrite-molar-ratio-as-a-measure-of-nitrite-reabsorption-in-experimental-and-clinical-settings
#17
Dimitrios Tsikas, Erik Hanff, Alexander Bollenbach, Ruan Kruger, Vu Vi Pham, Kristine Chobanyan-Jürgens, Dirk Wedekind, Tanja Arndt, Anne Jörns, Jimmy F P Berbée, Hans M G Princen, Thomas Lücke, François Mariotti, Jean-François Huneau, Stefan Ückert, Jürgen C Frölich, Sigurd Lenzen
We recently found that renal carbonic anhydrase (CA) is involved in the reabsorption of inorganic nitrite (NO2 - ), an abundant reservoir of nitric oxide (NO) in tissues and cells. Impaired NO synthesis in the endothelium and decreased NO bioavailability in the circulation are considered major contributors to the development and progression of renal and cardiovascular diseases in different conditions including diabetes. Isolated human and bovine erythrocytic CAII and CAIV can convert nitrite to nitrous acid (HONO) and its anhydride N2 O3 which, in the presence of thiols (RSH), are further converted to S-nitrosothiols (RSNO) and NO...
May 4, 2018: Amino Acids
https://www.readbyqxmd.com/read/29728396/application-of-genetic-epidemiology-to-cetp-cholesteryl-ester-transfer-protein-concentration-and-risk-of-cardiovascular-disease
#18
EDITORIAL
Tony R Merriman
No abstract text is available yet for this article.
May 2018: Circulation. Genomic and precision medicine
https://www.readbyqxmd.com/read/29728394/cetp-cholesteryl-ester-transfer-protein-concentration-a-genome-wide-association-study-followed-by-mendelian-randomization-on-coronary-artery-disease
#19
Lisanne L Blauw, Ruifang Li-Gao, Raymond Noordam, Renée de Mutsert, Stella Trompet, Jimmy F P Berbée, Yanan Wang, Jan B van Klinken, Tim Christen, Diana van Heemst, Dennis O Mook-Kanamori, Frits R Rosendaal, J Wouter Jukema, Patrick C N Rensen, Ko Willems van Dijk
BACKGROUND: We aimed to identify independent genetic determinants of circulating CETP (cholesteryl ester transfer protein) to assess causal effects of variation in CETP concentration on circulating lipid concentrations and cardiovascular disease risk. METHODS: A genome-wide association discovery and replication study on serum CETP concentration were embedded in the NEO study (Netherlands Epidemiology of Obesity). Based on the independent identified variants, Mendelian randomization was conducted on serum lipids (NEO study) and coronary artery disease (CAD; CARDIoGRAMplusC4D consortium)...
May 2018: Circulation. Genomic and precision medicine
https://www.readbyqxmd.com/read/29726048/role-of-glycans-in-cholesteryl-ester-transfer-protein-revealed-by-md-simulation
#20
Dongxiao Hao, Zhiwei Yang, Teng Gao, Zhiqi Tian, Lei Zhang, Shengli Zhang
Current cholesteryl ester transfer protein (CETP) inhibitors are designed based on the unglycosylated crystal structure, and most of them have failed to cure cardiovascular disease (CVD). It is particularly important for us to investigate the glycosylation structure of CETP (CETP-G) and effect of glycans on the structure and function of CETP. Here, we used a total of 3.0-μs molecular dynamics trajectories of nascent structure of CETP (CETP-N) and CETP-G to study their structural differentiations, to shed new light on the CETP-mediated lipid exchange...
May 3, 2018: Proteins
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