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https://www.readbyqxmd.com/read/28729361/cetp-cholesteryl-ester-transfer-protein-inhibition-with-anacetrapib-decreases-production-of-lipoprotein-a-in-mildly-hypercholesterolemic-subjects
#1
Tiffany Thomas, Haihong Zhou, Wahida Karmally, Rajasekhar Ramakrishnan, Stephen Holleran, Yang Liu, Patricia Jumes, John A Wagner, Brian Hubbard, Stephen F Previs, Thomas Roddy, Amy O Johnson-Levonas, David E Gutstein, Santica M Marcovina, Daniel J Rader, Henry N Ginsberg, John S Millar, Gissette Reyes-Soffer
OBJECTIVE: Lp(a) [lipoprotein (a)] is composed of apoB (apolipoprotein B) and apo(a) [apolipoprotein (a)] and is an independent risk factor for cardiovascular disease and aortic stenosis. In clinical trials, anacetrapib, a CETP (cholesteryl ester transfer protein) inhibitor, causes significant reductions in plasma Lp(a) levels. We conducted an exploratory study to examine the mechanism for Lp(a) lowering by anacetrapib. APPROACH AND RESULTS: We enrolled 39 participants in a fixed-sequence, double-blind study of the effects of anacetrapib on the metabolism of apoB and high-density lipoproteins...
July 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28711866/identification-of-apob-100-peptide-specific-cd8-t-cells-in-atherosclerosis
#2
Paul C Dimayuga, Xiaoning Zhao, Juliana Yano, Wai Man Lio, Jianchang Zhou, Peter M Mihailovic, Bojan Cercek, Prediman K Shah, Kuang-Yuh Chyu
BACKGROUND: T cells are found in atherosclerotic plaques, with evidence supporting a potential role for CD8+ T cells in atherogenesis. Prior studies provide evidence of low-density lipoprotein and apoB-100 reactive T cells, yet specific epitopes relevant to the disease remain to be defined. The current study was undertaken to identify and characterize endogenous, antigen-specific CD8+ T cells in atherosclerosis. METHODS AND RESULTS: A peptide fragment of apoB-100 that tested positive for binding to the mouse MHC-I allele H2K(b) was used to generate a fluorescent-labeled H2K(b) pentamer and tested in apoE(-/-) mice...
July 15, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28702990/the-relationship-of-amphipathic-beta-structures-in-the-beta-1-domain-of-apolipoprotein-b-to-the-properties-of-the-secreted-lipoprotein-particles-in-mca-rh7777-cells
#3
Medha Manchekar, Richa Kapil, Zhihuan Sun, Jere P Segrest, Nassrin Dashti
Our previous studies demonstrated that the first 1000 amino acid residues (the βα1 domain) of human apolipoprotein (apo) B-100, referred to as apoB:1000, are required for the initiation of lipoprotein assembly and the formation of a monodisperse stable phospholipid (PL)-rich particle. The objectives of this study were to: a) assess the effects on the properties of apoB truncates undergoing sequential inclusion of the amphipathic β strands in the N-terminal 700 residues of the β1 domain of apoB-100, and b) identify the subdomain in the β1 domain that is required for the formation of a microsomal triglyceride transfer protein (MTP)-dependent triacylglycerol (TAG)-rich apoB-containing particle...
July 13, 2017: Biochemistry
https://www.readbyqxmd.com/read/28692480/association-of-plasminogen-activator-inhibitor-1-and-low-density-lipoprotein-heterogeneity-as-a-risk-factor-of-atherosclerotic-cardiovascular-disease-with-triglyceride-metabolic-disorder-a-pilot-cross-sectional-study
#4
Kiyoshi Iida, Shigemasa Tani, Wataru Atsumi, Tsukasa Yagi, Kenji Kawauchi, Naoya Matsumoto, Atsushi Hirayama
BACKGROUND: We hypothesized that an increase in plasminogen activator inhibitor 1 (PAI-1) might reduce low-density lipoprotein (LDL) particle size in conjunction with triglyceride (TG) metabolism disorder, resulting in an increased risk of atherosclerotic cardiovascular disease (ASCVD). METHODS: This study was carried out as a hospital-based cross-sectional study in 537 consecutive outpatients (mean age: 64 years; men: 71%) with one or more risk factors for ASCVD from April 2014 to October 2014 at the Cardiovascular Center of Nihon University Surugadai Hospital...
July 7, 2017: Coronary Artery Disease
https://www.readbyqxmd.com/read/28673336/cerebrospinal-fluid-biomarkers-for-alzheimer-s-and-vascular-disease-vary-by-age-gender-and-apoe-genotype-in-cognitively-normal-adults
#5
Ge Li, Jane B Shofer, Eric C Petrie, Chang-En Yu, Charles W Wilkinson, Dianne P Figlewicz, Andrew Shutes-David, Jing Zhang, Thomas J Montine, Murray A Raskind, Joseph F Quinn, Douglas R Galasko, Elaine R Peskind
BACKGROUND: This study sought to evaluate gender and APOE genotype-related differences in the concentrations of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) and cerebrovascular injury across the life span of cognitively normal adults. METHODS: CSF amyloid beta1-42 (Aβ42), phospho-tau-181 (p-tau181), and total tau were measured in 331 participants who were between the ages of 21 and 100. CSF E-selectin and vascular cell adhesion protein 1 (VCAM1) were measured in 249 participants who were between the ages of 50 and 100...
July 3, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28572160/oxidized-phospholipids-and-risk-of-calcific-aortic-valve-disease-the-copenhagen-general-population-study
#6
Pia R Kamstrup, Ming-Yow Hung, Joseph L Witztum, Sotirios Tsimikas, Børge G Nordestgaard
OBJECTIVE: Lipoprotein(a) is causally associated with calcific aortic valve disease (CAVD). Lipoprotein(a) carries proinflammatory and procalcific oxidized phospholipids (OxPL). We tested whether the CAVD risk is mediated by the content of OxPL on lipoprotein(a). APPROACH AND RESULTS: A case-control study was performed within the Copenhagen General Population Study (n=87 980), including 725 CAVD cases (1977-2013) and 1413 controls free of cardiovascular disease...
June 1, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28527325/dyslipidemia-management-update
#7
REVIEW
Yingzi Chang, Jacques Robidoux
Association of hypercholesterolemia and atherosclerotic cardiovascular disease (ASCVD) is well established. Reducing low-density lipoprotein-cholesterol (LDL-C) and raising high-density lipoprotein-cholesterol (HDL-C) have been the therapeutic targets to reduce the risk of ASCVD. Cholesterol-lowering medications have been used to provide both primary and secondary prevention of ASCVD for many years by reducing the absorption and reabsorption, promoting excretion, or decreasing the synthesis of cholesterol. Within the past five years, several new classes of cholesterol-lowering drugs have been tested and approved for patients with hypercholesterolemia that are not well controlled by conventional therapy (ezetimibe, bile-acid sequestrants, and statins)...
April 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28463548/effects-of-oolonghomobisflavan-a-on-oxidation-of-low-density-lipoprotein
#8
Enkhtsetseg Sukhbold, Shogo Sekimoto, Emiko Watanabe, Akane Yamazaki, Lifeng Yang, Mikako Takasugi, Koji Yamada, Ryota Hosomi, Kenji Fukunaga, Hirofumi Arai
Oxidation of low-density lipoprotein (LDL) by reactive oxygen species (ROS) and reactive nitrogen species (RNS) has been suggested to be involved in the onset of atherosclerosis. Oolong tea contains unique polyphenols including oolonghomobisflavan A (OFA). In this study, the effects of OFA on LDL oxidation by ROS and RNS were investigated in vitro. OFA suppressed formation of cholesterol ester hydroperoxides in LDL oxidized by peroxyl radical and peroxynitrite, and formation of thiobarbituric acid reactive substances in LDL oxidized by Cu(2+)...
May 2, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28379594/pyrrolizidine-alkaloids-enhance-alcohol-induced-hepatocytotoxicity-in-vitro-in-normal-human-hepatocytes
#9
M G Neuman, L B Cohen, V Steenkamp
OBJECTIVE: Herbal remedies containing pyrrilidozine alkaloids (PA)s can induce liver damage, including hepato-sinusoidal obstruction syndrome (HSOS) or veno-occlusive liver disease (VOD). Some individuals misusing alcohol consume also teas and/or herbal remedies containing PA. The interaction or additive toxicity of alcohol to PA toxicity needs to be addressed. The objectives of this study are 1) to review the scientific literature on the PA-induced liver toxicity; 2) identify possible mechanism(s) involved in PA-induced hepatocytotoxicity in the presence or absence of ethanol (EtOH) in vitro in normal human hepatocytes (NHH) in primary culture...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28356880/cardiovascular-risk-factors-in-7-13-years-old-children-from-vojvodina-serbia
#10
Darko D Dželajlija, Slavica S Spasić, Jelena M Kotur-Stevuljevic, Nataša B Bogavac-Stanojevic
BACKGROUND: Atherosclerosis is a chronic inflammatory disease which starts early in life and depends on many factors, an important one being dyslipoproteinemia. According to several studies, atherosclerotic plaques or their precursors could be seen in children younger than 10 years. During later life, interaction with a sedentary way of life, as well as unhealthy nutrition, smoking, alcohol consumption, obesity and family history of cardiovascular disease cause the burden of atherosclerotic disease...
September 2016: Journal of Medical Biochemistry
https://www.readbyqxmd.com/read/28280493/t-cells-specific-for-a-self-peptide-of-apob-100-exacerbate-aortic-atheroma-in-murine-atherosclerosis
#11
Michael K Shaw, Kevin Y Tse, Xiaoqing Zhao, Kathryn Welch, Daniel T Eitzman, Raghavendar R Thipparthi, Paul C Montgomery, Ryan Thummel, Harley Y Tse
On the basis of mouse I-A(b)-binding motifs, two sequences of the murine apolipoprotein B-100 (mApoB-100), mApoB-1003501-3515 (designated P3) and mApoB-100978-992 (designated P6), were found to be immunogenic. In this report, we show that P6 is also atherogenic. Immunization of Apoe(-/-) mice fed a high-fat diet (HFD) with P6 resulted in enhanced development of aortic atheroma as compared to control mice immunized with an irrelevant peptide MOG35-55 or with complete Freund's adjuvant alone. Adoptive transfer of lymph node cells from P6-immunized donor mice to recipients fed an HFD caused exacerbated aortic atheromas, correlating P6-primed cells with disease development...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28274961/lipid-and-lipoprotein-abnormalities-in-acute-lymphoblastic-leukemia-survivors
#12
Sophia Morel, Jade Leahy, Maryse Fournier, Benoit Lamarche, Carole Garofalo, Guy Grimard, Floriane Poulain, Edgard Delvin, Caroline Laverdière, Maja Krajinovic, Simon Drouin, Daniel Sinnett, Valérie Marcil, Emile Levy
Survivors of acute lymphoblastic leukemia (ALL), the most common cancer in children, are at increased risk of developing late cardiometabolic conditions. However, the mechanisms are not fully understood. This study aimed to characterize the plasma lipid profile, Apo distribution, and lipoprotein composition of 80 childhood ALL survivors compared with 22 healthy controls. Our results show that, despite their young age, 50% of the ALL survivors displayed dyslipidemia, characterized by increased plasma triglyceride (TG) and LDL-cholesterol, as well as decreased HDL-cholesterol...
May 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28173800/oxidized-ldl-induced-jab1-influences-nf-%C3%AE%C2%BAb-independent-inflammatory-signaling-in-human-macrophages-during-foam-cell-formation
#13
Anja Schwarz, Gabriel A Bonaterra, Hans Schwarzbach, Ralf Kinscherf
BACKGROUND: Oxidized low-density lipoprotein (oxLDL) mediates the transformation of macrophages (MΦ) to cholesterol-rich foam cells and the release of pro-inflammatory cytokines during atherogenesis. JAB1 (Jun activation domain binding protein-1) is present in all stages of human plaques, involved in the Toll-like receptor-mediated activation of p38 mitogen-activated protein kinase (MAPK) and controls nuclear factor-kappa B (NF-κB) activation. Thus, we were interested in the role of JAB1 during foam cell formation of MΦ after oxLDL exposition...
February 7, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28028493/mutation-detection-in-chinese-patients-with-familial-hypercholesterolemia
#14
Ran Du, Liang-Liang Fan, Min-Jie Lin, Zhi-Jian He, Hao Huang, Ya-Qin Chen, Jing-Jing Li, Kun Xia, Shui-Ping Zhao, Rong Xiang
BACKGROUND: Familial hypercholesterolemia (FH) is the first molecularly and clinically characterized genetic disease of lipid metabolism. It is an autosomal dominant disorder with significantly elevated levels of total cholesterol and low density of lipoprotein cholesterol in serum, which would lead to extensive xanthomas and premature coronary heart disease. Mutations in low density lipoprotein receptor (LDLR), proprotein convertase subtilisin/kexin type 9 and Apo lipoprotein B-100 (APOB) have been identified to be the underlying cause of this disease...
2016: SpringerPlus
https://www.readbyqxmd.com/read/28019668/monosialyl-ganglioside-gm3-decreases-apolipoprotein-b-100-secretion-in-liver-cells
#15
Hyunju Choi, Un-Ho Jin, Sung-Koo Kang, Fukushi Abekura, Jun-Young Park, Kyung-Min Kwon, Seok-Jong Suh, Seung-Hak Cho, Ki-Tae Ha, Young-Coon Lee, Tae-Wook Chung, Cheorl-Ho Kim
Some sialic acid-containing glycolipids are known to regulate development of atherosclerosis with accumulated plasma apolipoprotein B-100 (Apo-B)-containing lipoproteins, because Apo-B as an atherogenic apolipoprotein is assembled mainly in VLDL and LDL. Previously, we have elucidated that disialyl GD3 promotes the microsomal triglyceride transfer protein (MTP) gene expression and secretion of triglyceride (TG)-assembled ApoB, claiming the GD3 role in ApoB lipoprotein secretion in liver cells. In the synthetic pathway of gangliosides, GD3 is synthesized by addition of a sialic acid residue to GM3...
August 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27956003/lipid-modifying-efficacy-and-tolerability-of-anacetrapib-added-to-ongoing-statin-therapy-in-patients-with-hypercholesterolemia-or-low-high-density-lipoprotein-cholesterol
#16
RANDOMIZED CONTROLLED TRIAL
Christie M Ballantyne, Sukrut Shah, Uma Kher, John A Hunter, Geraldine G Gill, Michael D Cressman, Tanya B Ashraf, Amy O Johnson-Levonas, Yale B Mitchel
To assess the effects of anacetrapib added to statin ± other lipid-modifying therapies in patients with hypercholesterolemia and not at their low-density lipoprotein cholesterol (LDL-C) goal (as per National Cholesterol Education Program Adult Treatment Panel III [NCEP ATP III] guidelines) and in those with low high-density lipoprotein cholesterol (HDL-C). Patients on a stable dose of moderate/high-intensity statin ± other lipid-modifying therapies with LDL-C ≥70, ≥100, ≥130, or ≥160 mg/dl for very high, high, moderate, and low coronary heart disease risk, respectively, or at LDL-C goal with HDL-C ≤40 mg/dl, were randomized 1:1:1, stratified by background therapy use, to anacetrapib 100 mg (n = 153), anacetrapib 25 mg (n = 152), or placebo (n = 154) for 24 weeks, followed by a 12-week off-drug reversal phase...
February 1, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/27941065/factorial-effects-of-evolocumab-and-atorvastatin-on-lipoprotein-metabolism
#17
RANDOMIZED CONTROLLED TRIAL
Gerald F Watts, Dick C Chan, Ricardo Dent, Ransi Somaratne, Scott M Wasserman, Rob Scott, Sally Burrows, P Hugh R Barrett
BACKGROUND: Monoclonal antibodies against proprotein convertase subtilisin kexin type 9 (PCSK9), such as evolocumab, lower plasma low-density lipoprotein (LDL)-cholesterol concentrations. Evolocumab is under investigation for its effects on cardiovascular outcomes in statin-treated, high-risk patients. The mechanism of action of PCSK9 monoclonal antibodies on lipoprotein metabolism remains to be fully evaluated. Stable isotope tracer kinetics can effectively elucidate the mode of action of new lipid-regulating pharmacotherapies...
January 24, 2017: Circulation
https://www.readbyqxmd.com/read/27935250/apolipoprotein-e-epsilon-genotype-has-a-greater-impact-on-apob-48-than-apob-100-responses-to-dietary-fat-manipulation-insights-from-the-satgen%C3%AE%C2%B5-study
#18
Kim G Jackson, Stacey Lockyer, Andrew L Carvalho-Wells, Christine M Williams, Anne M Minihane, Julie A Lovegrove
SCOPE: To determine the contribution of intestinally and liver-derived lipoproteins to the postprandial plasma triacylglycerol (TAG) response in APOE3/E3 and E3/E4 individuals following chronic dietary fat manipulation. METHODS AND RESULTS: In sequential order, participants (n = 12 E3/E3, n = 11 E3/E4) followed low fat; high-fat, high-saturated fat (HSF); and HSF with 3.45 g/day docosahexaenoic acid (HSF-DHA) diets, each for 8 weeks. After each dietary period, an acute test meal with a macronutrient profile representative of the dietary intervention was consumed...
December 9, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27891330/evaluation-of-lipid-profile-and-apolipoproteins-in-essential-hypertensive-patients
#19
Parsuram Nayak, Suchismita Panda, Pravat Kumar Thatoi, Roma Rattan, Srikrushna Mohapatra, Pramila Kumari Mishra
INTRODUCTION: Essential hypertension is one of the most common diseases of the Indian population contributing greatly to the morbidity, mortality and economic burden. It has a strong association with cardiovascular disease and abnormal lipid metabolism. Not only the traditional lipid parameters, but also the novel lipid components like Apo A1 and Apo B100 also have been identified to play a role. AIM: The present study was done to evaluate serum lipid profile and Apo A1, Apo B 100 in essential hypertensive patients and correlate their values with the degree of hypertension...
October 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/27738104/mycobacterium-tuberculosis-malate-synthase-structures-with-fragments-reveal-a-portal-for-substrate-product-exchange
#20
Hsiao-Ling Huang, Inna V Krieger, Maloy K Parai, Vijay B Gawandi, James C Sacchettini
Fragment screening and high throughput screening are complementary approaches that combine with structural biology to explore the binding capabilities of an active site. We have used a fragment-based approach on malate synthase (GlcB) from Mycobacterium tuberculosis and discovered several novel binding chemotypes. In addition, the crystal structures of GlcB in complex with these fragments indicated conformational changes in the active site that represent the enzyme conformations during catalysis. Additional structures of the complex with malate and of the apo form of GlcB supported that hypothesis...
December 30, 2016: Journal of Biological Chemistry
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