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Apolipoprotein E

Mads Rosenkilde, Lisbeth Rygaard, Pernille Nordby, Lars Bo Nielsen, Bente Stallknecht
Exercise training and weight loss both reduce cardiovascular risk, but the independent importance of the two strategies is unclear. We aimed to investigate independent and combined effects of exercise training and weight loss on lipoproteins and dyslipidemia in overweight sedentary men. Sixty individuals were randomized to 12 weeks of endurance training (T), energy-reduced diet (D), training and energy increased diet (T-iD), or control (C). Equal energetic deficits (-600 kcal/day) were prescribed by exercise for T and caloric restriction for D...
March 15, 2018: Journal of Applied Physiology
Mary Guaraldi, Thomas B Shea
Objective: We examined genetic and dietary challenge on hippocampal oxidative damage. Mice expressing (ApoE+/+) or lacking apolipoprotein E (ApoE-/-) were maintained on a standard diet or a high fat /high cholesterol (challenge) diet for 11-31 weeks. Similar levels of oxidative species were observed for ApoE+/+ and -/- mice maintained on the basal diet. Method: However, treatment of ApoE-/- homogenates with hydrogen peroxide and iron increased oxidative species by >100%, indicating an equivalent amount of potential oxidative species in latent form...
2018: Open Neurology Journal
Santiago Roura, Ana Gámez-Valero, Josep Lupón, Carolina Gálvez-Montón, Francesc E Borràs, Antoni Bayes-Genis
Dilated cardiomyopathy (DCM) remains a major cause of heart failure and carries a poor prognosis despite important advances in recent years. Better disease characterization using novel molecular techniques is needed to refine its progression. This study explored the proteomic signature of plasma-derived extracellular vesicles (EVs) obtained from DCM patients and healthy controls using size-exclusion chromatography (SEC). EV-enriched fractions were analyzed by liquid chromatography-mass spectrometry (LC-MS/MS)...
March 14, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Laura Lopez-Sanz, Susana Bernal, Carlota Recio, Iolanda Lazaro, Ainhoa Oguiza, Ana Melgar, Luna Jimenez-Castilla, Jesus Egido, Carmen Gomez-Guerrero
Oxidative stress resulting from excessive production of reactive oxygen species (ROS) or impaired antioxidant defenses is closely related to the development of diabetic vascular complications, including nephropathy and atherosclerosis. Chronic activation of Janus kinase/Signal transducer and activator of transcription (JAK/STAT) signaling pathway contributes to diabetic complications by inducing expression of genes involved in cell proliferation, fibrosis, inflammation, and oxidative stress. Suppressors of cytokine signaling (SOCS) family of endogenous JAK/STAT regulators is an attractive target for therapeutic intervention...
March 14, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Valentin Blanchard, Stephane Ramin-Mangata, Stephanie Billon-Crossouard, Audrey Aguesse, Manon Durand, Kevin Chemello, Brice Nativel, Laurent Flet, Maud Chetiveaux, David Jacobi, Jean-Marie Bard, Khadija Ouguerram, Gilles Lambert, Michel Krempf, Mikael Croyal
Human apolipoprotein E (apoE) exhibits three major isoforms (apoE2, apoE3, and apoE4) corresponding to polymorphism in the APOE gene. Total plasma apoE concentrations are closely related to these isoforms but the underlying mechanisms are unknown. We aimed to describe the kinetics of apoE individual isoforms to explore the mechanisms for variable total apoE plasma concentrations. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to discriminate between isoforms by identifying specific peptide sequences in subjects (3 E2/E3, 3 E3/E3 and 3 E3/E4 phenotypes) who received a primed constant infusion of2 H3 -leucine for 14 hours...
March 14, 2018: Journal of Lipid Research
Christine Contini, Martin Jansen, Brigitte König, Filiz Markfeld-Erol, Mirjam Kunze, Stefan Zschiedrich, Ulrich Massing, Irmgard Merfort, Heinrich Prömpeler, Ulrich Pecks, Karl Winkler, Gerhard Pütz
BACKGROUND: Preeclampsia is a life-threatening disease in pregnancy, and its complex pathomechanisms are poorly understood. In preeclampsia, lipid metabolism is substantially altered. In late onset preeclampsia, remnant removal disease like lipoprotein profiles have been observed. Lipid apheresis is currently being explored as a possible therapeutic approach to prolong preeclamptic pregnancies. Here, apheresis-induced changes in serum lipid parameters are analyzed in detail and their implications for preeclamptic lipid metabolism are discussed...
March 14, 2018: Lipids in Health and Disease
Jennifer L Etnier, William B Karper, Jeffrey D Labban, Aaron T Piepmeier, Chia-Hao Shih, William N Dudley, Vincent C Henrich, Laurie Wideman
Background: Alzheimer's disease is a progressive disease that degrades cognitive functioning and ultimately results in death. Currently, there is no cure for Alzheimer's disease and, hence, the identification of preventative strategies is important. Physical activity (PA) is a behavioral intervention that holds promise with respect to delaying the onset of Alzheimer's disease. Purpose: The purpose of this study was to explore the differential cognitive benefits achieved in response to PA as a function of a person's genetic risk for AD...
February 5, 2018: Annals of Behavioral Medicine: a Publication of the Society of Behavioral Medicine
Liv Tybjærg Nordestgaard, Anne Tybjærg-Hansen, Katrine Laura Rasmussen, Børge G Nordestgaard, Ruth Frikke-Schmidt
BACKGROUND: Clusterin, also known as apolipoprotein J (apoJ), is one of the most abundantly expressed apolipoproteins in the brain after apolipoprotein E (apoE). Like the ε4 allele of the apolipoprotein E gene (APOE), the clusterin gene (CLU) is a risk locus for Alzheimer's disease, and may play additional roles in atherosclerosis pathogenesis. We tested whether genetic variation in CLU was associated with either Alzheimer's disease or atherosclerosis-related diseases. METHODS: We studied individual data on 103,987 participants from the Copenhagen General Population Study (CGPS) and the Copenhagen City Heart Study (CCHS)...
March 14, 2018: BMC Medicine
Hee Kyoung Joo, Sunga Choi, Yu Ran Lee, Eun Ok Lee, Myoung Soo Park, Kyu Been Park, Cuk-Seong Kim, Yong Pyo Lim, Jong-Tae Park, Byeong Hwa Jeon
Anthocyanins, the most prevalent flavonoids in red/purple fruits and vegetables, are known to improve immune responses and reduce chronic disease risks. In this study, the anti-inflammatory activities of an anthocyanin-rich extract from red Chinese cabbage (ArCC) were shown based on its inhibitory effects in cultured endothelial cells and hyperlipidemic apolipoprotein E -deficient mice. ArCC treatment suppressed monocyte adhesion to tumor necrosis factor-α-stimulated endothelial cells. This was validated by ArCC's ability to downregulate the expression and transcription of endothelial adhesion molecules, determined by immunoblot and luciferase promoter assays, respectively...
March 12, 2018: International Journal of Molecular Sciences
Diego Z Carvalho, Erik K St Louis, David S Knopman, Bradley F Boeve, Val J Lowe, Rosebud O Roberts, Michelle M Mielke, Scott A Przybelski, Mary M Machulda, Ronald C Petersen, Clifford R Jack, Prashanthi Vemuri
Importance: Aging is associated with excessive daytime sleepiness (EDS), which has been linked to cognitive decline in the elderly. However, whether EDS is associated with the pathologic processes of Alzheimer disease remains unclear. Objective: To investigate whether EDS at baseline is associated with a longitudinal increase in regional β-amyloid (Aβ) accumulation in a cohort of elderly individuals without dementia. Design, Setting, and Participants: This prospective analysis included participants enrolled in the Mayo Clinic Study of Aging, a longitudinal population-based study in Olmsted County, Minnesota...
March 12, 2018: JAMA Neurology
Martha Lappas, Harry M Georgiou, Anida Velagic, Jane C Willcox, Michael Permezel, Alexis Shub
AIMS: The risk of developing type 2 diabetes is greater in women with previous gestational diabetes mellitus (GDM). Apolipoprotein (Apo) species have been associated with the development of type 2 diabetes in the general population. The aim of this study was to determine if circulating levels of Apo species can predict development of type 2 diabetes in women with previous GDM. METHODS: Apo AI, Apo AII, Apo B, Apo CII, Apo CIII and Apo E levels were measured in 95 women with normal glucose tolerance, 12 weeks following an index GDM pregnancy...
March 12, 2018: Experimental and Clinical Endocrinology & Diabetes
Kelsey R Thomas, Joel Eppig, Emily C Edmonds, Diane M Jacobs, David J Libon, Rhoda Au, David P Salmon, Mark W Bondi
OBJECTIVE: Preclinical Alzheimer's disease (AD) defined by a positive AD biomarker in the presence of normal cognition is presumed to precede mild cognitive impairment (MCI). Subtle cognitive deficits and cognitive inefficiencies in preclinical AD may be detected through process and error scores on neuropsychological tests in those at risk for progression to MCI. METHOD: Cognitively normal participants (n = 525) from the Alzheimer's Disease Neuroimaging Initiative were followed for up to 5 years and classified as either stable normal (n = 305) or progressed to MCI (n = 220)...
February 2018: Neuropsychology
Katia Pane, Mariavittoria Verrillo, Angela Avitabile, Elio Pizzo, Mario Varcamonti, Anna Zanfardino, Antimo Di Maro, Camilla Rega, Angela Amoresano, Viviana Izzo, Alberto Di Donato, Valeria Cafaro, Eugenio Notomista
Peptides with an N-terminal cysteine residue allow site-specific modification of proteins and peptides and chemical synthesis of proteins. They have been widely used to develop new strategies for imaging, drug discovery, diagnostics and chip technologies. Here we present a method to produce recombinant peptides with an N-terminal cysteine residue as a convenient alternative to chemical synthesis. The method is based on the release of the desired peptide from a recombinant fusion protein by mild acid hydrolysis of an Asp-Cys sequence...
March 12, 2018: Bioconjugate Chemistry
A Mattina, D Rosenbaum, R Bittar, D Bonnefont-Rousselot, D Noto, M Averna, E Bruckert, P Giral
BACKGROUND AND AIM: Lipoprotein-associated phospholipase A2 (Lp-PLA2 ) plays a key role in atherosclerosis development. It is considered a marker of increased risk of cardiovascular disease (CVD) and plaque vulnerability. Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated plasma levels of low-density lipoprotein cholesterol and a higher prevalence of early CVD. Our aim was to evaluate the differences in Lp-PLA2 activity in a population of hypercholesterolemic patients with and without definite FH...
February 2, 2018: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
Po-Jung Pao, Eszter Emri, Safiya Bishar Abdirahman, Talha Soorma, Hui-Hui Zeng, Stefanie M Hauck, Richard B Thompson, Imre Lengyel
Population-based and interventional studies have shown that elevated zinc levels can reduce the progression to advanced age-related macular degeneration. The objective of this study was to assess whether elevated extracellular zinc has a direct effect on retinal pigment epithelial cells (RPE), by examining the phenotype and molecular characteristics of increased extracellular zinc on human primary RPE cells. Monolayers of human foetal primary RPE cells were grown on culture inserts and maintained in medium supplemented with increasing total concentrations of zinc (0, 75, 100, 125 and 150 μM) for up to 4 weeks...
March 1, 2018: Journal of Trace Elements in Medicine and Biology
Kwun Kei Ng, Yingwei Qiu, June Chi-Yan Lo, Evelyn Siew-Chuan Koay, Woon-Puay Koh, Michael Wei-Liang Chee, Juan Zhou
We investigated the influence of the apolipoprotein E-ɛ4 allele (APOE-ɛ4) on longitudinal age-related changes in brain functional connectivity (FC) and cognition, in view of mixed cross-sectional findings. One hundred and twenty-two healthy older adults (aged 58-79; 25 APOE-ɛ4 carriers) underwent task-free fMRI scans at baseline. Seventy-eight (16 carriers) had at least one follow-up (every 2 years). Changes in intra- and internetwork FCs among the default mode (DMN), executive control (ECN), and salience (SN) networks, as well as cognition, were quantified using linear mixed models...
March 8, 2018: Human Brain Mapping
J W Gause, R J Day, C A Caraway, W W Poon, T T Rohn
Recent studies have supported a role for the proteolytic cleavage of apolipoprotein E4 (APOE4) as a potential mechanism for the enhanced dementia risk associated with Alzheimer's disease. To determine whether APOE4 fragmentation is correlated with AD, ELISA assays were performed with cerebral spinal fluid (CSF) and plasma samples utilizing an antibody that specifically detects a 17 kDa amino-terminal fragment (p17) of APOE (nApoECF antibody). In CSF samples, levels of APOE fragmentation were minimal in both neuropathological normals (NPNs) and AD cases and there were no significant differences between the two cohorts across APOE genotypes...
September 2017: Journal of Neurology and Neurological Disorders
Pascal J H Kusters, Tom T P Seijkens, Linda Beckers, Dirk Lievens, Holger Winkels, Vivian de Waard, Adriaan Duijvestijn, Moritz Lindquist Liljeqvist, Joy Roy, Alan Daugherty, Andrew Newby, Norbert Gerdes, Esther Lutgens
OBJECTIVE: The mechanisms underlying formation of arterial aneurysms remain incompletely understood. Because inflammation is a common feature during the progressive degeneration of the aortic wall, we studied the role of the costimulatory molecule CD40L, a major driver of inflammation, in aneurysm formation. APPROACH AND RESULTS: Transcriptomics data obtained from human abdominal aortic aneurysms and normal aortas revealed increased abundance of both CD40L and CD40 in media of thrombus-free and thrombus-covered human abdominal aortic aneurysms samples...
March 8, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Xue-Na Zheng, Jun Yang, Tao Xie, Bin Guo, Zhi-Qiang Xie, Li-Na Xie, Xue-Fen Wu, Gang-Zhu Hu, Mai-Lan Liu, Zeng-Hui Yue
OBJECTIVE: To observe the effect of herbal cake-separated moxibustion on blood lipid-apoprotein levels and the expression of Toll-like receptor 2 (TLR 2), TLR 4 and nuclear factor kappa B(NF-κB) mRNAs in atherosclerotic (AS) vulnerable plaques of hyperglycemia rabbits, so as to explore its mechanism underlying improvement of atherosclerosis. METHODS: Sixty New Zealand rabbits were randomly divided into 5 groups: control, model, direct moxibustion, herbal-cake-separated moxibustion and medication groups( n =12 rabbits in each group)...
February 25, 2018: Zhen Ci Yan Jiu, Acupuncture Research
Ling Li, Fan Zeng, Yu-Hui Liu, Hui-Yun Li, Shu-Yang Dong, Ze-Yan Peng, Yan-Jiang Wang, Hua-Dong Zhou
Polymorphisms of the cholesterol-24S-hydroxylase (CYP46A1) and apolipoprotein E (APOE) genes are risk factors for Alzheimer's disease (AD). Plasma level of 24S-hydroxcholesterol (24-OHC), the metabolite of cholesterol, is thought to correlate with AD. The present study investigated the correlation between these genetic factors and blood 24-OHC and amyloid-beta (Aβ) levels in AD patients. Association analysis, logistic regression, and linear regression were used to analyze the correlation of CYP46A1 and APOE genotypes with blood 24-OHC and Aβ levels and AD risk...
March 7, 2018: Molecular Neurobiology
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