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Apo b

K Lakota, D Hrušovar, M Ogrič, K Mrak-Poljšak, S Čučnik, M Tomšič, B Božič, P Žigon, S Sodin-Semrl
Background: RA patients have a higher incidence of cardiovascular diseases compared to the general population. Serum amyloid A (SAA) is an acute-phase protein, upregulated in sera of RA patients. Aim: To determine the effects of medications on SAA-stimulated human coronary artery endothelial cells (HCAEC). Methods: HCAEC were preincubated for 2 h with medications from sterile ampules (dexamethasone, methotrexate, certolizumab pegol, and etanercept), dissolved in medium (captopril) or DMSO (etoricoxib, rosiglitazone, meloxicam, fluvastatin, and diclofenac)...
2018: Mediators of Inflammation
Ru Zhang, Shufen Han, Zheng Zhang, Weiguo Zhang, Jing Yang, Zhongxiao Wan, Liqiang Qin
Cereal fiber is associated with decreasing the risk of cardiovascular diseases. However, whether cereal fiber modulates inflammatory response and improves atherosclerosis remains unclear. This study evaluated the anti-atherosclerotic effect of cereal fibers from oat or wheat bran and explored the potential anti-inflammatory mechanisms. Male ApoE-/- mice were given a high fat/cholesterol (HFC) diet, HFC diet supplemented with 0.8% oat fiber or wheat bran fiber. After 18 weeks of feeding period, serum lipids and inflammatory cytokines were measured...
April 17, 2018: Journal of Agricultural and Food Chemistry
Timothy A Couttas, Nupur Kain, Collin Tran, Zac Chatterton, John B Kwok, Anthony S Don
The greatest risk factor for developing Alzheimer's disease (AD) is aging. The major genetic risk factor for AD is the ɛ4 allele of the APOE gene, encoding the brain's major lipid transport protein, apolipoprotein E (ApoE). The research community is yet to decipher why the ApoE4 variant pre-disposes to AD, and how aging causes the disease. Studies have shown deregulated levels of sphingolipids, including decreased levels of the neuroprotective signaling lipid sphingosine 1-phosphate (S1P), and increased ceramide content, in brain tissue and serum of people with pre-clinical or very early AD...
April 11, 2018: Journal of Alzheimer's Disease: JAD
Michelle M Mielke, Clinton E Hagen, Jing Xu, Xiyun Chai, Prashanthi Vemuri, Val J Lowe, David C Airey, David S Knopman, Rosebud O Roberts, Mary M Machulda, Clifford R Jack, Ronald C Petersen, Jeffrey L Dage
INTRODUCTION: We examined and compared plasma phospho-tau181 (pTau181) and total tau: (1) across the Alzheimer's disease (AD) clinical spectrum; (2) in relation to brain amyloid β (Aβ) positron emission tomography (PET), tau PET, and cortical thickness; and (3) as a screening tool for elevated brain Aβ. METHODS: Participants included 172 cognitively unimpaired, 57 mild cognitively impaired, and 40 AD dementia patients with concurrent Aβ PET (Pittsburgh compound B), tau PET (AV1451), magnetic resonance imaging, plasma total tau, and pTau181...
April 4, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Branko Srećković, Ivan Soldatovic, Emina Colak, Igor Mrdovic, Mirjana Sumarac-Dumanovic, Hristina Janeski, Nenad Janeski, Jasna Gacic, Vesna Dimitrijevic-Sreckovic
BACKGROUND: Abdominal adiposity has a central role in developing insulin resistance (IR) by releasing pro-inflammatory cytokines. Patients with metabolic syndrome (MS) have higher values of homocysteine. Hyperhomocysteinemia correlates with IR, increasing the oxidative stress. Oxidative stress causes endothelial dysfunction, hypertension and atherosclerosis. The objective of the study was to examine the correlation of homocysteine with siMS score and siMS risk score and with other MS co-founding factors...
April 6, 2018: Drug Metabolism and Personalized Therapy
Indu Dhar, Vegard Lysne, Reinhard Seifert, Gard F T Svingen, Per M Ueland, Ottar K Nygård
BACKGROUND AND AIMS: Methionine (Met) is an essential amino acid involved in methylation reactions and lipid metabolism. A Met-deficient diet may cause hepatic lipid accumulation, which is considered an independent risk factor for atherosclerosis. However, the prospective relationship between circulating Met and incident acute myocardial infarction (AMI) is unknown. METHODS: We studied the associations of plasma Met and incident AMI in 4156 patients (77% men; median age 62 years) with stable angina pectoris, among whom the majority received lipid lowering therapy with statins...
March 23, 2018: Atherosclerosis
Ma Teresa Pellicer Martinez, Ana Bermejo Martinez, Jason C Crack, John D Holmes, Dimitri A Svistunenko, Andrew W B Johnston, Myles R Cheesman, Jonathan D Todd, Nick E Le Brun
Rhizobial iron regulator A (RirA) is a global regulator of iron homeostasis in many nitrogen-fixing Rhizobia and related species of α-proteobacteria. It belongs to the widespread Rrf2 super-family of transcriptional regulators and features three conserved Cys residues that characterise the binding of an iron-sulfur cluster in other Rrf2 family regulators. Here we report biophysical studies demonstrating that RirA contains a [4Fe-4S] cluster, and that this form of the protein binds RirA-regulated DNA, consistent with its function as a repressor of expression of many genes involved in iron uptake...
December 1, 2017: Chemical Science
Shu-Chao Pang, Li Peng, Jun-Ping Zhang, Yuan-Yuan Wang, Hui-Yun Jia, Li-Yuan Bi, Mei-Ling Chen
Bushenkangshuai tablet (BSKS) is a Chinese herbal compound which has been used for the treatment of cardiovascular and cerebrovascular diseases in China for decades. This study intends to explore the molecular mechanism of BSKS against atherosclerosis in ApoE-/- mice. ApoE-/- mice were fed with western-type diet for 6 weeks and then were given BSKS for 6 weeks. The results showed that BSKS attenuated the size of the atherosclerotic lesion, reduced visceral adipose content, and decreased blood lipids. We also found that BSKS promoted the expression of adiponectin and its receptors, inhibited the expression of Toll-like receptor 4 and nuclear factor-kappa B, decreased the levels of interleukin-1 beta, monocyte chemotactic protein-1, and vascular cell adhesion molecule-1, and increased the levels of interleukin-10 and adiponectin...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
Elzbieta Pac-Kozuchowska, Paulina Krawiec, Ewelina Grywalska
BACKGROUND: The aim of the study was to evaluate serum parameters of lipid metabolism, homocysteine, soluble adhesion molecules and common carotid artery wall thickness in children from families with early symptoms of atherosclerosis. METHODS: The first stage included 137 pairs of mothers and newborns, and the second 18 children from the same group (age 18-30 months) and their parents (age 21-46 years) with a history of premature coronary artery disease (CAD), as well as 12 age- and sex-matched controls...
April 3, 2018: BMC Pediatrics
Jared B Shaw, Mikhail Gorshkov, Qinghao Wu, Ljiljana Paša-Tolić
Mass spectrometric characterization of large biomolecules, such as intact proteins, requires the specificity afforded by ultra-high resolution mass measurements performed at both the intact mass and product ion levels. Although the performance of time-of-flight mass analyzers is steadily increasing, the choice of mass analyzer for large biomolecules (e.g. proteins >50 kDa) is generally limited to the Fourier transform family of mass analyzers, such as Orbitrap and ion cyclotron resonance (FTICR-MS) with the latter providing unmatched mass resolving power and measurement accuracy...
April 3, 2018: Analytical Chemistry
Nupur Bansal, Zheng Zheng, Lin Frank Song, Jun Pei, Kenneth M Merz
Obtaining a detailed description of how active site flap motion affects substrate or ligand binding will advance structure-based drug design (SBDD) efforts on systems including the kinases, HSP90, HIV protease, ureases, etc. Through this understanding we will be able to design better inhibitors and better proteins that have desired functions. Herein we address this issue by generating the relevant configurational states of a protein flap on the molecular energy landscape using an approach we call MTFlex-b and then following this with a procedure to estimate the free energy associated with the motion of the flap region...
April 2, 2018: Journal of the American Chemical Society
Niklas Mattsson, Colin Groot, Willemijn J Jansen, Susan Landau, Victor Villemagne, Sebastiaan Engelborghs, Mark Mintun, Alberto Lleo, José Luis Molinuevo, William Jagust, Giovanni B Frisoni, Adrian Ivanoiu, Gaël Chételat, Catarina Resende de Oliveira, Karen M Rodrigue, Johannes Kornhuber, Anders Wallin, Aleksandra Klimkowicz-Mrowiec, Ramesh Kandimella, Julius Popp, Pauline P Aalten, Dag Aarsland, Daniel Alcolea, Ina S Almdahl, Inês Baldeiras, Mark A van Buchem, Enrica Cavedo, Kewei Chen, Ann D Cohen, Stefan Förster, Juan Fortea, Kristian S Frederiksen, Yvonne Freund-Levi, Kiran Dip Gill, Olymbia Gkatzima, Timo Grimmer, Harald Hampel, Sanna-Kaisa Herukka, Peter Johannsen, Koen van Laere, Mony de Leon, Wolfgang Maier, Jan Marcusson, Olga Meulenbroek, Hanne M Møllergård, John C Morris, Barbara Mroczko, Arto Nordlund, Sudesh Prabhakar, Oliver Peters, Lorena Rami, Eloy Rodríguez-Rodríguez, Catherine M Roe, Eckart Rüther, Isabel Santana, Johannes Schröder, Sang W Seo, Hilkka Soininen, Luiza Spiru, Erik Stomrud, Hanne Struyfs, Charlotte E Teunissen, Frans R J Verhey, Stephanie J B Vos, Linda J C van Waalwijk van Doorn, Gunhild Waldemar, Åsa K Wallin, Jens Wiltfang, Rik Vandenberghe, David J Brooks, Tormod Fladby, Christopher C Rowe, Alexander Drzezga, Marcel M Verbeek, Marie Sarazin, David A Wolk, Adam S Fleisher, William E Klunk, Duk L Na, Pascual Sánchez-Juan, Dong Young Lee, Agneta Nordberg, Magda Tsolaki, Vincent Camus, Juha O Rinne, Anne M Fagan, Henrik Zetterberg, Kaj Blennow, Gil D Rabinovici, Oskar Hansson, Bart N M van Berckel, Wiesje M van der Flier, Philip Scheltens, Pieter Jelle Visser, Rik Ossenkoppele
INTRODUCTION: Apolipoprotein E (APOE) ε4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid β (Aβ) pathology. METHODS: We included 3451 Aβ+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE ε4 prevalence in relation to age, sex, education, and geographical location...
March 27, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Fan Liao, Aimin Li, Monica Xiong, Nga Bien-Ly, Hong Jiang, Yin Zhang, Mary Beth Finn, Rosa Hoyle, Jennifer Keyser, Katheryn B Lefton, Grace O Robinson, Javier Remolina Serrano, Adam P Silverman, Jing L Guo, Jennifer Getz, Kirk Henne, Cheryl Eg Leyns, Gilbert Gallardo, Jason D Ulrich, Patrick M Sullivan, Eli Paul Lerner, Eloise Hudry, Zachary K Sweeney, Mark S Dennis, Bradley T Hyman, Ryan J Watts, David M Holtzman
The apolipoprotein E E4 allele of the APOE gene is the strongest genetic factor for late-onset Alzheimer disease (LOAD). There is compelling evidence that apoE influences Alzheimer disease (AD) in large part by affecting amyloid β (Aβ) aggregation and clearance; however, the molecular mechanism underlying these findings remains largely unknown. Herein, we tested whether anti-human apoE antibodies can decrease Aβ pathology in mice producing both human Aβ and apoE4, and investigated the mechanism underlying these effects...
March 30, 2018: Journal of Clinical Investigation
Gillian Douglas, Ashley B Hale, Jyoti Patel, Surawee Chuaiphichai, Ayman Al Haj Zen, Victoria S Rashbrook, Lucy Trelfa, Mark J Crabtree, Eileen McNeill, Keith M Channon
Introduction: GTP cyclohydrolase I (GTPCH) catalyses the first and rate-limiting reaction in the synthesis of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide synthases (NOS). Both eNOS and iNOS have been implicated in the progression of atherosclerosis, with opposing effects in eNOS and iNOS knockout mice. However, the pathophysiologic requirement for BH4 in regulating both eNOS and iNOS function, and the effects of loss of BH4 on the progression of atherosclerosis remains unknown...
March 27, 2018: Cardiovascular Research
Takayuki Kimura, Kouji Kobiyama, Holger Winkels, Kevin Tse, Jacqueline Miller, Melanie Vassallo, Dennis Wolf, Christian Ryden, Marco Orecchioni, Thamotharampillai Dileepan, Marc K Jenkins, Eddie A James, William W Kwok, David B Hanna, Robert C Kaplan, Howard D Strickler, Helen G Durkin, Seble G Kassaye, Roksana Karim, Phyllis C Tien, Alan L Landay, Stephen J Gange, John Sidney, Alessandro Sette, Klaus Ley
Background -CD4+ T cells play an important role in atherosclerosis, but their antigen specificity is poorly understood. Immunization with apolipoprotein B (ApoB, core protein of low density lipoprotein) is known to be atheroprotective in animal models. Here, we report on a human APOB peptide, p18, that is sequence-identical in mouse ApoB and binds to both mouse and human MHC-II. Methods -We constructed p18-tetramers to detect human and mouse APOB-specific T cells and assayed their phenotype by flow cytometry including CD4 lineage transcription factors, intracellular cytokines, and TCR activation...
March 27, 2018: Circulation
Constanze Sommer, Casseday P Richers, Wolfgang Lubitz, Thomas B Rauchfuss, Edward J Reijerse
The active site of the [FeFe]-hydrogenases features a binuclear [2Fe]H sub-cluster that contains a unique bridging amine moiety close to an exposed iron center. Heterolytic splitting of H2 results in the formation of a transient terminal hydride at this iron site, which, however is difficult to stabilize. We show that the hydride intermediate forms immediately when [2Fe]H is replaced with [2Ru]H analogues through artificial maturation. Outside the protein, the [2Ru]H analogues form bridging hydrides, which rearrange to terminal hydrides after insertion into the apo-protein...
March 26, 2018: Angewandte Chemie
Arpita Basu, Alicia J Jenkins, Julie A Stoner, Ying Zhang, Richard L Klein, Maria F Lopes-Virella, W Timothy Garvey, David S Schade, Jamie Wood, Petar Alaupovic, Timothy J Lyons
Circulating apolipoprotein-defined lipoprotein subclasses (ADLS) and apolipoproteins predict vascular events in the general and type 2 diabetes populations, but data in type 1 diabetes (T1DM) are limited. We examined associations of ADLS, serum apolipoproteins and conventional lipids with carotid IMT measured contemporaneously and six years later in 417 T1DM participants (men: n=269, age 42±6 y [mean±SD]; women: n=148, age 39±8 y) in the Epidemiology of Diabetes Interventions and Complications study, the follow-up of the Diabetes Control and Complications Trial (DCCT)...
March 25, 2018: Journal of Lipid Research
Nicholas J Viney, Calvin Yeang, Xiaohong Yang, Shuting Xia, Joseph L Witztum, Sotirios Tsimikas
BACKGROUND: The laboratory measurement of "low-density lipoprotein cholesterol (LDL-C)" includes the cholesterol content of lipoprotein(a) (Lp(a)-C). OBJECTIVE: To estimate the "true" LDL-C in relation to changes in apolipoprotein B-100 (apoB-100) and assess changes in proprotein convertase subtilisin/kexin 9 (PCSK9) levels in patients with elevated Lp(a) treated with IONIS-APO(a)Rx. METHODS: A pooled placebo group (n = 29), and cohort A (n = 24, baseline Lp(a) 50-175 mg/dL) and cohort B (n = 8, baseline Lp(a) > 175 mg/dL) treated with IONIS-APO(a)Rx were studied...
March 1, 2018: Journal of Clinical Lipidology
Xue Dong, Weina Zhang, Haiyan Wu, Jinyan Huang, Ming Zhang, Pengran Wang, Hao Zhang, Zhu Chen, Sai-Juan Chen, Guoyu Meng
Oncogenic fusions are major drivers in leukemogenesis and may serve as potent targets for treatment. DUX4/IGHs have been shown to trigger the abnormal expression of ERGalt through binding to DUX4-Responsive-Element (DRE), which leads to B-cell differentiation arrest and a full-fledged B-ALL. Here, we determined the crystal structures of Apo- and DNADRE -bound DUX4HD2 and revealed a clamp-like transactivation mechanism via the double homeobox domain. Biophysical characterization showed that mutations in the interacting interfaces significantly impaired the DNA binding affinity of DUX4 homeobox...
March 15, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Polyxeni Mantani, Pontus Dunér, Eva Bengtsson, Irena Ljungcrantz, Lena Sundius, Fong To, Jan Nilsson, Harry Björkbacka, Gunilla Nordin Fredrikson
Atherosclerosis is a chronic inflammatory disease characterized by the entrapment of apolipoprotein B-containing lipoproteins in the arterial intima leading to local inflammation. T helper (Th) cell 1-mediated immune responses have been associated with atherosclerosis, and the cytokine interleukin-25 (IL-25 or IL-17E) has been reported to potentially regulate Th1 cell- and Th17 cell-related immune responses. In this study, we evaluated the effects of complete IL-25 deficiency or of a temporal IL-25 blockade on atherosclerosis development in apolipoprotein E-deficient (Apoe-/-) mice...
March 23, 2018: Journal of Biological Chemistry
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