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apo B 100

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 go hand in hand with structural biology to explore the binding capabilities of an active site and to provide diversity for inhibitor design. We used fragment-based approaches 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 hypothesized to represent states the enzyme assumes in the substrate-product exchange during catalysis...
October 13, 2016: Journal of Biological Chemistry
Nicholas J Viney, Julian C van Capelleveen, Richard S Geary, Shuting Xia, Joseph A Tami, Rosie Z Yu, Santica M Marcovina, Steven G Hughes, Mark J Graham, Rosanne M Crooke, Stanley T Crooke, Joseph L Witztum, Erik S Stroes, Sotirios Tsimikas
BACKGROUND: Elevated lipoprotein(a) (Lp[a]) is a highly prevalent (around 20% of people) genetic risk factor for cardiovascular disease and calcific aortic valve stenosis, but no approved specific therapy exists to substantially lower Lp(a) concentrations. We aimed to assess the efficacy, safety, and tolerability of two unique antisense oligonucleotides designed to lower Lp(a) concentrations. METHODS: We did two randomised, double-blind, placebo-controlled trials...
September 21, 2016: Lancet
V N Titov
In phylogenesis, becoming of biologicalfunctions and biological reactions proceeds with the purpose ofpermanent increasing of "kinetic perfection ". The main role belongs to factors ofphysical, chemical and biological kinetics, their evaluation using systemic approach technique under permanent effect of natural selection. The late-in-phylogenesis insulin, proceeded with, in development of biological function of locomotion, specialization of insulin-dependent cells: skeletal myocytes, syncytium of cardiomyocytes, subcutaneous adipocytes, periportal hepatocytes, Kupffer's macrophages and β-cells of islets of pancreas...
February 2016: Klinicheskaia Laboratornaia Diagnostika
Françoise Proust, Olivia Drescher, Elhadji A Laouan-Sidi, Elizabeth Robinson, Michel Lucas, Éric Dewailly
BACKGROUND: n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) from fish are known modulators of cardiometabolic risk factors. OBJECTIVE: To examine fatty acids (FAs) status and the relationship between n-3 LC-PUFA and cardiometabolic risk factors in Cree participants. DESIGN: We analyzed data from a cross-sectional study (n=829) conducted in Cree adults (aged 18-74 years) from 7 communities of the James Bay territory of Quebec (Canada) in 2005-2009...
2016: International Journal of Circumpolar Health
Chun-Lin Lee, Ja-Yan Wen, Ya-Wen Hsu, Tzu-Ming Pan
BACKGROUND/PURPOSES: Monascin (MS) and ankaflavin (AK) produced by Monascus purpureus NTU 568 were proven to show excellent hypolipidemic effects in our previous studies; however, the mechanism is still unclear. METHODS: This study used MS, AK, and monacolin K as test substances and performed tests on rats fed high-fat and high-cholesterol diet for 8 weeks. The lipid levels and the related protein levels of the rats were assessed to understand the effects of MS, AK, and monacolin K on lipid metabolism...
June 24, 2016: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
Marco Gentile, Rosario Peluso, Matteo Nicola Dario Di Minno, Luisa Costa, Francesco Caso, Biagio de Simone, Gabriella Iannuzzo, Raffaele Scarpa, Paolo Rubba
Psoriatic arthritis (PsA) is an inflammatory rheumatic disorder occurring in patients with psoriasis. Several studies have shown an association between Psa and traditional atherosclerotic risk factors. We evaluated the relationship between small dense low-density lipoproteins particles (sd-LDL) a risk marker for atherosclerosis, sub-clinical atherosclerosis and PsA in a group of 50 patients with PsA and in 100 controls. Cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides, insulin, homeostasis model assessment (HOMA), Apo B, and sd-LDL have been measured...
August 2016: Clinical Rheumatology
Anand Srivastava, Beverley Adams-Huet, Gloria L Vega, Robert D Toto
UNLABELLED: Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) can improve dyslipidemia in patients with diabetes and albuminuria. Whether combined ACEi+ARB or ACEi+mineralocorticoid receptor blockade improves dyslipidemia is not known. We hypothesized long-term administration of either losartan 100 mg or spironolactone 25 mg once daily added onto lisinopril 80 mg once daily would improve dyslipidemia in diabetic nephropathy (DN). We measured lipid levels, very-low-density (V), intermediate-density (I), low-density (LDL), high-density (HDL) lipoprotein, LDL particle size with their respective cholesterol (C) and apolipoprotein B levels (ApoB), and urine albumin/creatinine ratio (UACR) at 12-week interval during a 48-week randomized, double-blind placebo-controlled trial in 81 patients with DN...
August 2016: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
Anthony S Wierzbicki, Adie Viljoen
INTRODUCTION: Anti-sense oligonucleotide (ASO) therapies are a new development in clinical pharmacology offering greater specificity compared to small molecule inhibitors and the ability to target intracellular process' not susceptible to antibody-based therapies. AREAS COVERED: This article reviews the chemical biology of ASOs and related RNA therapeutics. It then reviews the data on their use to treat hyperlipidaemia. Data on mipomersen - an ASO to apolipoprotein B-100(apoB) licensed for treatment of homozygous familial hypercholesterolaemia (FH) is presented...
September 2016: Expert Opinion on Biological Therapy
V N Titov
The concepts of atherosclerosis as afatly acids pathology, deficiency syndrome in cells ofpolyene fatty acids were expounded in 1990. The spirits cholesterol and glycerin play integrated physical chemical function in fatly acids' metabolism in transforming polar fatty acids into such non-polar form as ethers cholesterol and triglycerides. The amount of fatty acids transferred by lipoproteins to triglycerides significantly exceeds amount of fatty acids as ethers cholesterol. The triglycerides dominate in cells and ethers cholesterol outside cells...
January 2016: Klinicheskaia Laboratornaia Diagnostika
Ya Jin, Jin Chen, Ahui Wang, Jun Zhang, Shumin Chen, Takashi Manabe, Wen Tan
The method of digitized native protein mapping, combining nondenaturing micro 2DE, grid gel-cutting, and quantitative LC-MS/MS (in data-independent acquisition mode, or MS(E) ), was improved by using a new MS/MS mode, ion mobility separation enhanced-MS(E) (HDMS(E) ), and applied to analyze the area of human plasma low-density lipoprotein (LDL). An 18 mm × 4.8 mm rectangular area which included LDL on a nondenaturing micro 2D gel of human plasma was grid-cut into 72 square gel pieces and subjected to quantitative LC-MS/MS...
July 2016: Electrophoresis
Hakan Timur, Halil Korkut Daglar, Ozgur Kara, Ayse Kirbas, Hasan Ali Inal, Gulenay Gencosmanoglu Turkmen, Zehra Yilmaz, Burak Elmas, Dilek Uygur
OBJECTIVE: To investigate Apo A-1 and Apo B-100 levels and Apo B-100/Apo A-1 ratios in preeclamptic (PE) patients. MATERIALS AND METHODS: Forty-eight PE and 48 without PE patients (healthy pregnancies) matched for gestational age were included. Maternal age, parity, gestational age at delivery, obstetrical complications including intrauterine growth restriction (IUGR) and gestational diabetes mellitus (GDM), serum Apo A-1 and Apo B-100 levels, and the Apo B-100/Apo A-1 ratio were compared...
April 2016: Pregnancy Hypertension
Paulette D Chandler, Yiqing Song, Jennifer Lin, Shumin Zhang, Howard D Sesso, Samia Mora, Edward L Giovannucci, Kathryn E Rexrode, M Vinayaga Moorthy, Chunying Li, Paul M Ridker, I-Min Lee, JoAnn E Manson, Julie E Buring, Lu Wang
BACKGROUND: Lipid biomarkers, such as HDL-cholesterol concentrations, have been shown to have positive, inverse, and null associations with total, breast, and colorectal cancer risks. Studies of novel lipid biomarkers, such as apolipoprotein A-I (apo A-I) and apolipoprotein B-100 (apo B-100), and cancer risk have been sparse, to our knowledge. OBJECTIVES: We evaluated the prospective association of total, breast, colorectal, and lung cancers and cancer mortality with circulating lipid biomarkers in 15,602 female health professionals in the Women's Health Study (aged ≥45 y, free of cardiovascular disease and cancer, and without hormone replacement therapy or lipid-lowering medications at baseline)...
June 2016: American Journal of Clinical Nutrition
Shun Ishibashi, Shizuya Yamashita, Hidenori Arai, Eiichi Araki, Koutaro Yokote, Hideki Suganami, Jean-Charles Fruchart, Tatsuhiko Kodama
BACKGROUND AND AIMS: To assess the efficacy and safety of K-877 (Pemafibrate), a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα) that possesses unique PPARα activity and selectivity, compared with placebo and fenofibrate in dyslipidaemic patients with high triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) levels. METHODS AND RESULTS: This study was a double blind, placebo-controlled, parallel-group 12-week clinical trial...
June 2016: Atherosclerosis
André J Tremblay, Benoît Lamarche, Jean-Charles Hogue, Patrick Couture
Dietary n-3 polyunsaturated fatty acids (PUFAs) have been proposed to modulate plasma lipids, lipoprotein metabolism, and inflammatory state and to reduce triglyceride (TG) concentrations. The present double-blind, randomized, placebo-controlled, crossover study investigated the effects of n-3 PUFA supplementation at 3 g/d for 8 weeks on the intravascular kinetics of intestinally derived apolipoprotein (apo) B-48-containing lipoproteins in 10 men with type 2 diabetes. In vivo kinetics of the TG-rich lipoprotein (TRL) apoB-48 and VLDL apoB-100 were assessed using a primed-constant infusion of L-[5,5,5-D3] leucine for 12 hours in a fed state...
2016: Journal of Diabetes Research
T A Rozhkova, V N Titov, V A Amelyushkina, S I Kaba, V V Kukhartchuk
According to phylogenetic theory of general pathology, the function of low density lipoproteins (LDL) and hydrolysis of triglycerides (TG) in them under the effect of hepatic glycerol hydrolase apoC-III (HGH) developed at much earlier stages of phylogenesis than functioning of insulin-dependent phylogenetically late very low density lipoproteins (VLDL). For millions ofyears, lipolysis and HGH+apoC-III have activated transfer of polyenic fatty acids (FA) in the form of cholesteryl polyesters (CLE) from high density lipoproteins (HDL) to linoleic and linolenic LDL under the effect of cholesteryl ester transfer protein...
December 2015: Klinicheskaia Laboratornaia Diagnostika
Violeta G Trusca, Adina D Mihai, Elena V Fuior, Ioana M Fenyo, Anca V Gafencu
AIM: To investigate the effect of high homocysteine (Hcy) levels on apolipoprotein E (apoE) expression and the signaling pathways involved in this gene regulation. METHODS: Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot were used to assess apoE expression in cells treated with various concentrations (50-500 μmol/L) of Hcy. Calcium phosphate-transient transfections were performed in HEK-293 and RAW 264.7 cells to evaluate the effect of Hcy on apoE regulatory elements [promoter and distal multienhancer 2 (ME2)]...
February 26, 2016: World Journal of Biological Chemistry
Margaret R Diffenderfer, Stefania Lamon-Fava, Santica M Marcovina, P Hugh R Barrett, Julian Lel, Gregory G Dolnikowski, Lars Berglund, Ernst J Schaefer
OBJECTIVES: Lipoprotein(a) [Lp(a)] is mainly similar in composition to LDL, but differs in having apolipoprotein (apo) (a) covalently linked to apoB-100. Our purpose was to examine the individual metabolism of apo(a) and apoB-100 within plasma Lp(a). MATERIALS AND METHODS: The kinetics of apo(a) and apoB-100 in plasma Lp(a) were assessed in four men with dyslipidemia [Lp(a) concentration: 8.9-124.7nmol/L]. All subjects received a primed constant infusion of [5,5,5-(2)H3] L-leucine while in the constantly fed state...
April 2016: Metabolism: Clinical and Experimental
Anjali Manocha, L M Srivastava
The current epidemic affecting Indians is coronary artery disease (CAD), and is currently one of the most common causes of mortality and morbidity in developed and developing countries. The higher rate of CAD in Indians, as compared to people of other ethnic origin, may indicate a possible genetic susceptibility. Hence, Lp(a), an independent genetic risk marker for atherosclerosis and cardiovascular disease assumes great importance. Lp(a), an atherogenic lipoprotein, contains a cholesterol rich LDL particle, one molecule of apolipoprotein B-100 and a unique protein, apolipoprotein (a) which distinguishes it from LDL...
March 2016: Indian Journal of Clinical Biochemistry: IJCB
Yan Zhang, Cheng-Gang Zhu, Yuan-Lin Guo, Sha Li, Rui-Xia Xu, Qian Dong, Jian-Jun Li
BACKGROUND: It has been proposed that plasma fibrinogen is associated with lipid levels and increased cardiovascular risk. However, the interrelationship has not been well-elucidated. We hypothesise that lipids may be potential mediators. METHODS: We enrolled 4748 consecutive subjects scheduled for coronary angiography in this study. The severity of coronary atherosclerosis was assessed by Gensini score (GS). By principle component analysis, a multi-marker lipid index was extracted weighting the coefficients of six atherogenic lipid parameters: total cholesterol (TC), low-density lipoprotein-cholesterol, non-high-density lipoprotein-cholesterol (non-HDL-C), apolipoprotein (apo) B, apoB/apoA1, and TC/HDL-C ratio...
June 2016: Heart, Lung & Circulation
Klaus Ley
Atherosclerosis is an inflammatory disease of the arterial wall. It is accompanied by an autoimmune response against apolipoprotein B-100, the core protein of low-density lipoprotein, which manifests as CD4 T cell and antibody responses. To assess the role of the autoimmune response in atherosclerosis, the nature of the CD4 T cell response against apolipoprotein B-100 was studied with and without vaccination with major histocompatibility complex-II-restricted apolipoprotein B-100 peptides. The immunologic basis of autoimmunity in atherosclerosis is discussed in the framework of theories of adaptive immunity...
March 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
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