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https://www.readbyqxmd.com/read/28432183/anacetrapib-driven-triglyceride-lowering-explained-the-fortuitous-role-of-cetp-in-the-intravascular-catabolism-of-triglyceride-rich-lipoproteins
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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...
April 10, 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
#8
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
#9
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
#10
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...
April 10, 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
#11
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...
April 6, 2017: Laboratory Medicine
https://www.readbyqxmd.com/read/28380664/chronic-administration-of-anacetrapib-is-associated-with-accumulation-in-adipose-and-slow-elimination
#12
Rajesh Krishna, Ferdous Gheyas, Yang Liu, David Hagen, Brittany Walker, Akshita Chawla, Josee Cote, Robert O Blaustein, David E Gutstein
Anacetrapib is a novel CETP inhibitor in late stage clinical development, shown in preceding clinical trials to have residual pharmacological activity after prolonged washout following chronic dosing. Preclinical findings suggests 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 1 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
#13
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
https://www.readbyqxmd.com/read/28376855/effects-of-the-sglt2-inhibitor-dapagliflozin-on-hdl-cholesterol-particle-size-and-cholesterol-efflux-capacity-in-patients-with-type-2-diabetes-a-randomized-placebo-controlled-trial
#14
Gian Paolo Fadini, Benedetta Maria Bonora, Giancarlo Zatti, Nicola Vitturi, Elisabetta Iori, Maria Cristina Marescotti, Mattia Albiero, Angelo Avogaro
BACKGROUND: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) reduce glucose levels, body weight, and blood pressure, possibly resulting in cardiovascular protection. In phase III trials, SGLT2i were shown to increase HDL cholesterol. We aimed to evaluate whether the SGLT2i dapagliflozin affects HDL function in a randomized placebo-controlled trial. METHODS: Thirty-three type 2 diabetic patients were randomized to receive dapagliflozin 10 mg or placebo for 12 weeks on top of their glucose lowering medications...
April 4, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28315561/polymorphisms-of-lipid-metabolism-enzyme-coding-genes-in-patients-with-diabetic-dyslipidemia
#15
Aslı Tetik Vardarlı, Ece Harman, Vildan Bozok Çetintaş, Meral Kayıkçıoğlu, Egemen Vardarlı, Ayhan Zengi, Ali Şahin Küçükaslan, Zuhal Eroğlu
OBJECTIVE: The polymorphisms/mutations of genes encoding proteins and enzymes involved in lipoprotein metabolism play important roles in the development of diabetic dyslipidemia. The aim of our study was to investigate the effects of LPL (rs320), LIPC (rs2070895), SCARB1 (rs5888), LCAT (rs2292318), CETP (rs708272), ADIPOQ (rs1501299), RETN (rs3745367), PON1 (rs662), and MNSOD (rs4880) gene polymorphisms on lipid metabolism and diabetic dyslipidemia. METHODS: This case-control study included 217 patients with diabetic dyslipidemia and 212 healthy age- and gender-matched individuals...
March 3, 2017: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/28314859/effects-of-cetp-inhibition-with-anacetrapib-on-metabolism-of-vldl-tg-and-plasma-apolipoproteins-c-ii-c-iii-and-e
#16
John S Millar, Michael E Lassman, Tiffany Thomas, Rajasekhar Ramakrishnan, Patricia Jumes, Richard L Dunbar, Emile M deGoma, Amanda L Baer, Wahida Karmally, Daniel S Donovan, Hashmi Rafeek, John A Wagner, Stephen Holleran, Joseph Obunike, Yang Liu, Soumia Aoujil, Taylor Standiford, David E Gutstein, Henry N Ginsberg, Daniel J Rader, Gissette Reyes-Soffer
Cholesteryl ester transfer protein (CETP) mediates the transfer of HDL cholesteryl esters(CE) for TG in VLDL/LDL. CETP inhibition, with anacetrapib, increases HDL-cholesterol(C), reduces LDL-C and lowers TG levels. This study describes the mechanisms responsible for TG lowering by examining the kinetics of VLDL-TG and apolipoproteins (apo) C-II, C-III, and E. Hypercholesterolemic subjects were randomized to either placebo(N=10) or atorvastatin 20 mg/qd(N=29) for 4 weeks(period 1) followed by 8-weeks of anacetrapib, 100 mg/qd(period 2)...
March 17, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28290785/-genetic-risk-factors-of-macrovascular-complications-in-patients-with-type-2-diabetes
#17
A A Bystrova, A S Ulitina, M V Kim, S A Skoryukova, V V Miroshnikova, A A Panteleeva, N A Korelskaya, Zhu He Zhu He, M A Nikolaev, S N Pchelina, E I Baranova, E I Krasilnikova
High risk of macrovascular complications in patients with type 2 diabetes mellitus (T2DM) is caused by insulin resistance and atherogenic dyslipidemia that may be genetically determined. The aim of this study was to assess the association of polymorphic genetic variants APOA5 (S19W/rs3135506), CETP (Taq1B/rs708272), PON1 (Q192R /rs662) and PPARG (Pro12Ala /rs1801282) with T2DM and macrovascular complications in patients with T2DM resident in Northwestern Russia. We examined 386 patients with T2DM and 199 healthy controls...
February 2017: Kardiologiia
https://www.readbyqxmd.com/read/28259941/consumption-of-policosanol-enhances-hdl-functionality-via-cetp-inhibition-and-reduces-blood-pressure-and-visceral-fat-in-young-and-middle-aged-subjects
#18
Jae-Yong Kim, Seong-Min Kim, Suk-Jeong Kim, Eun-Young Lee, Jae-Ryong Kim, Kyung-Hyun Cho
It is well-known that policosanol can improve serum lipid profiles, although the physiological mechanism is still unknown. Here, we investigated functional and structural changes in lipoproteins after consumption of policosanol. To investigate the physiological effect of policosanol, we analyzed serum parameters in young non-smoker (YN; n=7, 24.0±2.4 years), young smoker (YS; n=7, 26.3±1.5 years), and middle-aged subjects (MN; n=11, 52.5±9.8 years) who consumed policosanol daily (10 mg/day) for 8 weeks...
April 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28250428/genetic-contribution-to-lipid-levels-in-early-life-based-on-158-loci-validated-in-adults-the-family-study
#19
Shanice Christie, Sébastien Robiou-du-Pont, Sonia S Anand, Katherine M Morrison, Sarah D McDonald, Guillaume Paré, Stephanie A Atkinson, Koon K Teo, David Meyre
The contribution of polymorphisms associated with adult lipids in early life is unknown. We studied 158 adult lipid polymorphisms in 1440 participants (544 children, 544 mothers and 324 fathers) of the Family Atherosclerosis Monitoring In early life (FAMILY) birth cohort. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) measurements were collected at birth, 3 and 5 years of age. Polymorphisms were genotyped using the Illumina Cardio-Metabochip array...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28244718/apoe-and-cetp-taqib-polymorphisms-influence-metabolic-responses-to-hibiscus-sabdariffa-l-and-gynostemma-pentaphyllum-makino-tea-consumption-in-hypercholesterolemic-subjects
#20
Nutjaree Jeenduang, Boonnisa Sangkaew, Pacharee Chantaracha, Sirada Chanchareonsri, Thunyaluk Plyduang, Wanida Thitdee, Cathaleeya Samae, Wacharaporn Pitumanon
BACKGROUND AND OBJECTIVES: Hibiscus sabdariffa L. (HS) and Gynostemma pentaphyllum Makino (GP) have been used as traditional medicines to treat diabetes and hypercholesterolemia. Nevertheless, there is interindividual variation in the metabolic responses to HS and GP consumption. This may be due to genetic factors. The aim of this study was to investigate the effects of HS and GP tea consumption on anthropometric data, fasting blood glucose (FBG), and lipid concentrations in hypercholesterolemia subjects with different genotypes of the APOE and CETP TaqIB polymorphisms...
March 2017: Asia Pacific Journal of Clinical Nutrition
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