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Apo b

Yong-Ping Bai, Jia-Xiong Zhang, Quan Sun, Ji-Peng Zhou, Jing-Min Luo, Ling-Fang He, Xing-Chi Lin, Ling-Ping Zhu, Wan-Zhou Wu, Zhen-Yu Wang, Guo-Gang Zhang
Background -Nitrates are widely used to treat coronary artery disease, but their therapeutic value is compromised by nitrate tolerance, owing to the dysfunction of prostaglandin I2 synthase (PTGIS). Micro RNAs (miRNAs) repress target gene expression and are recognized as important epigenetic regulators of endothelial function. The aim of this study was to determine whether nitrates induce nitrovasodilator resistance via microRNA-dependent repression of PTGIS gene expression. Methods -Nitrovasodilator resistance was induced by nitroglycerin (GTN; 100 mg/kg/day, 3 days) infusion in Apoe-/- mice...
February 5, 2018: Circulation
Gaofeng Liang, Shu Kan, Yanliang Zhu, Shuying Feng, Wenpo Feng, Shegan Gao
Introduction: Exosomes are closed-membrane nanovesicles that are secreted by a variety of cells and exist in most body fluids. Recent studies have demonstrated the potential of exosomes as natural vehicles that target delivery of functional small RNA and chemotherapeutics to diseased cells. Methods: In this study, we introduce a new approach for the targeted delivery of exosomes loaded with functional miR-26a to scavenger receptor class B type 1-expressing liver cancer cells...
2018: International Journal of Nanomedicine
Alison Headley, Andres DeLeon-Benedetti, Chuanhui Dong, Bonnie Levin, David Loewenstein, Christian Camargo, Tatjana Rundek, Henrik Zetterberg, Kaj Blennow, Clinton B Wright, Xiaoyan Sun
OBJECTIVE: To determine whether high CSF levels of neurogranin (Ng) predict longitudinal decline in memory and executive function during early-stage Alzheimer disease (AD). METHODS: Baseline levels of CSF Ng were studied in relation to cross-sectional and longitudinal cognitive performance over 8 years. Data were obtained from the Alzheimer's Disease Neuroimaging Initiative database, and participants with normal cognition (n = 111) and mild cognitive impairment (MCI) (n = 193) were included...
February 2, 2018: Neurology
Qu Tian, Woei-Nan Bair, Susan M Resnick, Murat Bilgel, Dean F Wong, Stephanie A Studenski
BACKGROUND: Higher amyloid burden predicts gait slowing in aging. Whether and which gait characteristics are associated with amyloid burden is less clear. Gait variability may be more sensitive to amyloid burden than mean gait characteristics. METHODS: In the Baltimore Longitudinal Study of Aging, 99 older participants without neurological disease had concurrent amyloid imaging and assessment of gait characteristics. β-amyloid burden was measured using 11C-Pittsburgh compound B (PiB) positron emission tomography...
February 6, 2018: Gait & Posture
Simon H Bridge, Sabrina Pagano, Meleri Jones, Graham R Foster, Dermot Neely, Nicolas Vuilleumier, Margaret F Bassendine
BACKGROUND/PURPOSE: One to three per cent of the world's population has hepatitis C virus (HCV) infection, which is not only a major cause of liver disease and cancer but also associated with an increased risk of atherosclerosis, despite an ostensibly favourable lipid profile. Autoantibodies are frequent in HCV infection and emerging evidence shows that autoantibodies could be valuable for cardiovascular disease (CVD) risk stratification. This study investigated a novel independent biomarker of CVD, autoantibodies to apolipoprotein A-1 (anti-apoA-1 IgG) and lipids in patients with chronic HCV before, during and after direct-acting anti-viral (DAA) therapy...
February 8, 2018: Hepatology International
Saeed Ghobadi, Zahra Hassanzadeh-Rostami, Fatemeh Mohammadian, Arash Nikfetrat, Negar Ghasemifard, Hamidreza Raeisi Dehkordi, Shiva Faghih
OBJECTIVE: We aim to report a systematic review and meta-analysis of randomized controlled trials (RCTs) on effects of olive oil consumption compared with other plant oils on blood lipids. METHODS: PubMed, web of science, Scopus, ProQuest, and Embase were systematically searched until September 2017, with no age, language and design restrictions. Weighed mean difference (WMD) and 95% confidence interval (CI) were expressed as effect size. Sensitivity analyses and pre specified subgroup was conducted to evaluate potential heterogeneity...
February 8, 2018: Critical Reviews in Food Science and Nutrition
Fernanda Martins de Albuquerque, Mariana De Santis Filgueiras, Naruna Pereira Rocha, Ana Paula Pereira Castro, Luana Cupertino Milagres, Milene Cristine Pessoa, Sylvia do Carmo Castro Fransceschini, Juliana Farias de Novaes
The objective of the study was to assess the association between serum zinc level and cardiometabolic factors in prepubertal Brazilian children. This was a cross-sectional study in a representative sample of schoolchildren 8 to 9 years of age in public and private urban schools in Viçosa, Minas Gerais State, Brazil. Body composition was assessed with dual-energy x-ray absorptiometry. The study measured serum glucose, insulin, total cholesterol, high and low density lipoprotein cholesterol, triglycerides, apolipoproteins A (Apo A) and B, uric acid, leptin, homocysteine, ultrasenstive C-reactive protein, and serum zinc...
February 5, 2018: Cadernos de Saúde Pública
Jonathan B Rosenberg, Michael Kaplitt, Bishnu P De, Alvin Chen, Thomas Flagiello, Christiana O Salami, Eduard Pey, Lingzhi Zhao, Rodolfo Ricart Arbona, Sebastien Monette, Jonathan Dyke, Douglas Ballon, Stephen M Kaminsky, Dolan Sondhi, Gregory Petsko, Steven Paul, Ronald G Crystal
Alzheimer's disease (AD) is a progressive degenerative neurological disorder affecting nearly 1 in 9 elderly people in the United States. Population studies have shown that an inheritance of the apolipoprotein E (APOE) variant APOE4 allele increases the risk of developing AD, whereas, APOE2 homozygotes are protected from late onset AD. We hypothesized that expression of the "protective" APOE2 variant by genetic modification of the central nervous system (CNS) of APOE4 homozygotes could reverse or prevent progressive neurologic damage...
February 6, 2018: Human Gene Therapy. Clinical Development
Kun Ren, Xiao Zhu, Zhi Zheng, Zhong-Cheng Mo, Xiao-Shan Peng, Yong-Zhi Zeng, Han-Xiao Ou, Qing-Hai Zhang, Hui-Zhou Qi, Guo-Jun Zhao, Guang-Hui Yi
BACKGROUND AND AIMS: Liver scavenger receptor class B type I (SR-BI) exerts atheroprotective effects through selective lipid uptake (SLU) from high-density lipoprotein cholesterol (HDL-C). Low hepatic SR-BI expression leads to high HDL-C levels in the circulation and an increased risk of atherosclerosis. Furthermore, macrophage SR-BI mediates bidirectional cholesterol flux and may protect against atherogenesis. Previous studies have revealed that miR-24 is closely related to cardiovascular disease (CVD) progression...
January 30, 2018: Atherosclerosis
Tom T P Seijkens, Claudia M van Tiel, Pascal J H Kusters, Dorothee Atzler, Oliver Soehnlein, Barbara Zarzycka, Suzanne A B M Aarts, Marnix Lameijer, Marion J Gijbels, Linda Beckers, Myrthe den Toom, Bram Slütter, Johan Kuiper, Johan Duchene, Maria Aslani, Remco T A Megens, Cornelis van 't Veer, Gijs Kooij, Roy Schrijver, Marten A Hoeksema, Louis Boon, Francois Fay, Jun Tang, Samantha Baxter, Aldo Jongejan, Perry D Moerland, Gert Vriend, Boris Bleijlevens, Edward A Fisher, Raphael Duivenvoorden, Norbert Gerdes, Menno P J de Winther, Gerry A Nicolaes, Willem J M Mulder, Christian Weber, Esther Lutgens
BACKGROUND: Disrupting the costimulatory CD40-CD40L dyad reduces atherosclerosis, but can result in immune suppression. The authors recently identified small molecule inhibitors that block the interaction between CD40 and tumor necrosis factor receptor-associated factor (TRAF) 6 (TRAF-STOPs), while leaving CD40-TRAF2/3/5 interactions intact, thereby preserving CD40-mediated immunity. OBJECTIVES: This study evaluates the potential of TRAF-STOP treatment in atherosclerosis...
February 6, 2018: Journal of the American College of Cardiology
J K Chhetri, P de Souto Barreto, C Cantet, M Cesari, N Coley, S Andrieu, B Vellas
Defining the primary cognitive endpoint is a major decision for Alzheimer's disease preventive trials. As an example for further trials we present in detail the three-year cognitive decline in the placebo group of MAPT trial, a randomized controlled trial (RCT) using a cognitive composite score (MAPT-PACC). Participants were dementia-free adults 70 years or older, with subjective memory complaints. Our findings as expected showed subjects with older age (>75), higher beta amyloid brain deposition, APOE-ε4 allele carriers, with low RBC DHA+EPA levels and higher CDR level are at higher risk of cognitive decline...
2018: Journal of Prevention of Alzheimer's Disease
Rohanah Hussain, Charlotte S Hughes, Tamás Jávorfi, Giuliano Siligardi, Paul Williams, Boyan B Bonev
Thermal unfolding of proteins is used extensively in screening of drug candidates because molecular interactions with ligands and substrates affect strongly protein stability, transition temperature and cooperativity. We use synchrotron radiation circular dichroism to monitor the thermal evolution of secondary structure in proteins as they approach the melting point and the impact of substrate on their thermal behaviour. Using Landau free energy expansion, we quantify transition strength and proximity to a critical point through the relative separation τ+ between the transition temperature Tm and the spinodal T+, obtained from the equation of state...
February 5, 2018: Journal of Physical Chemistry. B
Kristen L Kelly, Shannon R Dalton, Rebecca B Wai, Kanika Ramchandani, Rosalind J Xu, Sara Linse, Casey H Londergan
Seven native residues on the regulatory protein calmodulin, including three key methionine residues, were replaced (one by one) by the vibrational probe amino acid cyanylated cysteine, which has a unique CN stretching vibration that reports on its local environment. Almost no perturbation was caused by this probe at any of the seven sites, as reported by CD spectra of calcium-bound calmodulin and binding thermodynamics for the formation of a complex between calmodulin and a canonical target peptide from skeletal muscle myosin light chain kinase measured by isothermal titration...
February 5, 2018: Journal of Physical Chemistry. A
Zahra Hajmohammadi, Mojtaba Heydari, Majid Nimrouzi, Pouya Faridi, Mohammad Javad Zibaeenezhad, Gholamhossein Ranjbar Omrani, Mesbah Shams
BACKGROUND: Lipid-lowering effect of Rhus coriaria L. (Rhus) has been investigated in multiple animal studies with promising results. Nonetheless, its clinical efficacy has not been adequately examined. OBJECTIVE: The aim of this study was to evaluate the lipid-lowering effects of Rhus among patients with hyperlipidemia. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: The study was designed as a two-arm, double-blind placebo-controlled randomized clinical trial, using a parallel design...
January 2018: Journal of Integrative Medicine
Hao Shu, Yongmei Shi, Gang Chen, Zan Wang, Duan Liu, Chunxian Yue, B Douglas Ward, Wenjun Li, Zhan Xu, Guangyu Chen, Qi-Hao Guo, Jun Xu, Shi-Jiang Li, Zhijun Zhang
The apolipoprotein E (APOE) ε4 and ε2 alleles are acknowledged genetic factors modulating Alzheimer's disease (AD) risk and episodic memory (EM) deterioration in an opposite manner. Mounting neuroimaging studies describe EM-related brain activity differences among APOE alleles but remain limited in elucidating the underlying mechanism. Here, we hypothesized that the APOE ε2, ε3, and ε4 alleles have distinct EM neural substrates, as a manifestation of degeneracy, underlying their modulations on EM-related brain activity and AD susceptibility...
February 2, 2018: Brain Imaging and Behavior
Min Feng, Daqian Xu, Lirui Wang
Background: Atherosclerosis, a chronic multi-factorial vascular disease, has become a predominant cause of a variety of cardiovascular disorders. miR-26a was previously reported to be involved in atherosclerosis progression. However, the underlying mechanism of miR-26a in atherosclerosis remains to be further explained. Methods: High-fat diet (HFD)-fed apolipoprotein E (apoE)-/- mice and oxidized low-density lipoprotein (ox-LDL)-stimulated human aortic endothelial cells (HAECs) were established as in vivo and in vitro models of atherosclerosis...
2018: Cell & Bioscience
Jean-Philippe Drouin-Chartier, André J Tremblay, Marie-Claude Lépine, Valéry Lemelin, Benoît Lamarche, Patrick Couture
Background: The substitution of omega (ω)-6 (n-6) polyunsaturated fatty acids (PUFAs) for saturated fatty acids (SFAs) is advocated in cardiovascular disease prevention. The impact of this substitution on lipoprotein metabolism in subjects with dyslipidemia associated with insulin resistance (IR) remains unknown. Objective: In men with dyslipidemia and IR, we evaluated the impact of substituting ω-6 PUFAs for SFAs on the in vivo kinetics of apolipoprotein (apo) B-containing lipoproteins and on the intestinal expression of key genes involved in lipoprotein metabolism...
January 1, 2018: American Journal of Clinical Nutrition
Mira Mäkelä, Karri Kaivola, Miko Valori, Anders Paetau, Tuomo Polvikoski, Andrew B Singleton, Bryan J Traynor, David J Stone, Terhi Peuralinna, Pentti J Tienari, Maarit Tanskanen, Liisa Myllykangas
Objective: To test the association of distinct neuropathologic features of Alzheimer disease (AD) with risk loci identified in genome-wide association studies. Methods: Vantaa 85+ is a population-based study that includes 601 participants aged ≥85 years, of which 256 were neuropathologically examined. We analyzed 29 AD risk loci in addition to APOE ε4, which was studied separately and used as a covariate. Genotyping was performed using a single nucleotide polymorphism (SNP) array (341 variants) and imputation (6,038 variants)...
February 2018: Neurology. Genetics
Rachel Golan, Iris Shai, Yftach Gepner, Ilana Harman-Boehm, Dan Schwarzfuchs, J David Spence, Grace Parraga, Dan Buchanan, Shula Witkow, Michael Friger, Idit F Liberty, Benjamin Sarusi, Sivan Ben-Avraham, Dana Sefarty, Nitzan Bril, Michal Rein, Noa Cohen, Uta Ceglarek, Joachim Thiery, Michael Stumvoll, Matthias Blüher, Meir J Stampfer, Assaf Rudich, Yaakov Henkin
BACKGROUND/OBJECTIVES: The progression of carotid-plaque volume in patients with type 2 diabetes is common. Previous observational studies showed an association between moderate alcohol and reduced risk of coronary disease. We examined whether consuming moderate wine affects the progression of carotid atherosclerosis. SUBJECTS/METHODS: In the CASCADE (CArdiovaSCulAr Diabetes and Ethanol), a 2-year randomized controlled trial, we randomized abstainers with type 2 diabetes were to drink 150 ml of either red wine, white wine, or water, provided for 2 years...
January 29, 2018: European Journal of Clinical Nutrition
Erfei Song, Sofhia V Ramos, Xiaojing Huang, Ying Liu, Amy Botta, Hye Kyoung Sung, Patrick C Turnbull, Michael B Wheeler, Thorsten Berger, Derek J Wilson, Christopher G R Perry, Tak W Mak, Gary Sweeney
Lipocalin-2 (Lcn2), a critical component of the innate immune response which binds siderophores and limits bacterial iron acquisition, can elicit spillover adverse proinflammatory effects. Here we show that holo-Lcn2 (Lcn2-siderophore-iron, 1:3:1) increases mitochondrial reactive oxygen species (ROS) generation and attenuates mitochondrial oxidative phosphorylation in adult rat primary cardiomyocytes in a manner blocked by N-acetyl-cysteine or the mitochondria-specific antioxidant SkQ1. We further demonstrate using siderophores 2,3-DHBA (2,3-dihydroxybenzoic acid) and 2,5-DHBA that increased ROS and reduction in oxidative phosphorylation are direct effects of the siderophore component of holo-Lcn2 and not due to apo-Lcn2 alone...
January 29, 2018: Proceedings of the National Academy of Sciences of the United States of America
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