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https://www.readbyqxmd.com/read/28651346/effect-of-apoe-%C3%AE%C2%B5-genotype-on-lipoprotein-a-and-the-associated-risk-of-myocardial-infarction-and-aortic-valve-stenosis
#1
Leonard Kritharides, Børge G Nordestgaard, Anne Tybjærg-Hansen, Pia R Kamstrup, Shoaib Afzal
Context: Lipoprotein(a) is a genetic risk factor for myocardial infarction and aortic valve stenosis. APOE ε2/3/4 genotypes affect plasma lipoprotein(a); however, the effects of APOE genotypes on the prediction of myocardial infarction and aortic valve stenosis by lipoprotein(a) are unknown. Objective: We tested the hypothesis that APOE ε2/3/4 genotype affects plasma lipoprotein(a), the contribution of plasma apoE levels this effect, and the associated risk of myocardial infarction and aortic valve stenosis...
June 23, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28650998/functional-annotation-of-alzheimer-s-disease-associated-loci-revealed-by-gwass
#2
Zengpeng Han, Han Huang, Yue Gao, Qingyang Huang
Genome-wide association studies (GWASs) discovered a number of SNPs and genes associated with Alzheimer's disease (AD). However, how these SNPs and genes influence the liability to AD is not fully understood. We deployed computational approaches to explore the function and action mechanisms of AD -related SNPs and genes identified by GWASs, including the effects of 195 GWAS lead SNPs and 338 proxy SNPs on miRNAs binding and protein phosphorylation, their RegulomeDB and 3DSNP scores, and gene ontology, pathway enrichment and protein-protein interaction network of 126 AD-associated genes...
2017: PloS One
https://www.readbyqxmd.com/read/28648916/long-term-changes-in-time-spent-walking-and-subsequent-cognitive-and-structural-brain-changes-in-older-adults
#3
John R Best, Caterina Rosano, Howard J Aizenstein, Qu Tian, Robert M Boudreau, Hilsa N Ayonayon, Suzanne Satterfield, Eleanor M Simonsick, Stephanie Studenski, Kristine Yaffe, Teresa Liu-Ambrose
Previous studies have shown that more active older adults have better cognition and brain health based on a variety of structural neuroimaging measures. Nevertheless, the effects of maintaining physical activity (PA) over an extended period of time on future changes in older adults' cognition and brain structure are unknown. Participants were 141 initially well-functioning community-dwelling older adults (aged 70-79 years at baseline; 60% female; 42% black) studied over a 13-year period. PA (self-reported time spent walking) was assessed annually from years 1 to 10...
June 6, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28648056/anamorsin-ndor1-complex-reduces-2fe-2s-mitoneet-via-a-transient-protein-protein-interaction
#4
Francesca Camponeschi, Simone Ciofi-Baffoni, Lucia Banci
Human mitoNEET is a homodimeric protein anchored to the outer mitochondrial membrane and with a C-terminal [2Fe-2S] binding domain located in the cytosol. Recently, human mitoNEET has been shown to be implicated in Fe/S cluster repair of the cytosolic iron regulatory protein 1 (IRP1), a key regulator of cellular iron homeostasis in mammalian cells. The Fe/S cluster repairing function of mitoNEET is based on a Fe/S redox switch mechanism: under normal cellular conditions, reduced [2Fe-2S](+) mitoNEET is present and is inactive as Fe/S cluster transfer protein; under conditions of oxidative cellular stress, the clusters of mitoNEET become oxidized and the formed [2Fe-2S](2+) mitoNEET species reacts promptly to initiate Fe/S cluster transfer to IRP1 recycling the cytosolic apo-IRP1 into holo-aconitase...
June 25, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28647612/evolution-of-human-apolipoprotein-e-apoe-isoforms-gene-structure-protein-function-and-interaction-with-dietary-factors
#5
REVIEW
Patricia Huebbe, Gerald Rimbach
Apolipoprotein E (APOE) is a member of the vertebrate protein family of exchangeable apolipoproteins that is characterized by amphipathic α-helices encoded by multiple nucleotide tandem repeats. Its equivalent in flying insects - apolipophorin-III - shares structural and functional commonalities with APOE, suggesting the possibility of an evolutionary relationship between the proteins. In contrast to all other known species, human APOE is functionally polymorphic and possesses three major allelic variants (ε4, ε3 and ε2)...
June 21, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28646901/effect-of-ezetimibe-add-on-therapy-over-52%C3%A2-weeks-extension-analysis-of-prospective-randomized-trial-research-study-in-type-2-diabetes-subjects
#6
Kentaro Sakamoto, Mitsunobu Kawamura, Takayuki Watanabe, Keiko Ashidate, Takahide Kohro, Akira Tanaka, Yasumichi Mori, Motoki Tagami, Tsutomu Hirano, Tsutomu Yamazaki, Teruo Shiba
BACKGROUND: Lowering cholesterol levels decreases the risk of atherosclerotic diseases. Effective ways to stably reduce LDL-C level are warranted in type 2 diabetic patients, a high-risk population for CVD, with various anti-diabetic therapeutic background. The RESEARCH study focuses on LDL-C reduction in this population along with modifications of the lipid profiles. We evaluated long-term ezetimibe add-on therapy in T2DM patients with hypercholesterolemia. METHODS: In a randomized, multicenter, open-label, prospective study, a total of 109 T2DM patients not attaining LDL-C target value despite first-line dose statin (10 mg of atorvastatin or 1 mg of pitavastatin) therapy in Japan were recruited...
June 24, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28646427/tanshinone-iia-attenuates-atherosclerosis-in-apolipoprotein-e-knockout-mice-infected-with-porphyromonas-gingivalis
#7
Yan Xuan, Yue Gao, Hao Huang, Xiaoxuan Wang, Yu Cai, Qing Xian Luan
Tanshinone IIA (TSA), a pharmacologically active component isolated from Danshen, may prevent cardiovascular diseases due to its anti-inflammatory, anti-oxidative, and anti-adipogenic effects. Porphyromonas gingivalis, a major periodontal pathogen, may contribute to the progression of atherosclerosis. Here, we studied the effects of TSA on atherosclerosis in ApoE(-/-) mice with P. gingivalis infection. Eight-week-old ApoE(-/-) mice were randomized to (a) phosphate-buffered saline (PBS), (b) P. gingivalis, and (c) P...
June 23, 2017: Inflammation
https://www.readbyqxmd.com/read/28646220/angiotensin-ii-synergizes-with-baff-to-promote-atheroprotective-regulatory-b-cells
#8
Padmapriya Ponnuswamy, Jeremie Joffre, Olivier Herbin, Bruno Esposito, Ludivine Laurans, Christoph J Binder, Thomas F Tedder, Lynda Zeboudj, Xavier Loyer, Andreas Giraud, Yujiao Zhang, Alain Tedgui, Ziad Mallat, Hafid Ait-Oufella
Angiotensin II (AngII) promotes hypertension, atherogenesis, vascular aneurysm and impairs post-ischemic cardiac remodeling through concerted roles on vascular cells, monocytes and T lymphocytes. However, the role of AngII in B lymphocyte responses is largely unexplored. Here, we show that chronic B cell depletion (Baffr deficiency) significantly reduces atherosclerosis in Apoe (-/-) mice infused with AngII. While adoptive transfer of B cells in Apoe (-/-) /Baffr (-/-) mice reversed atheroprotection in the absence of AngII, infusion of AngII in B cell replenished Apoe (-/-) /Baffr (-/-) mice unexpectedly prevented the progression of atherosclerosis...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28645636/theobromine-does-not-affect-postprandial-lipid-metabolism-and-duodenal-gene-expression-but-has-unfavorable-effects-on-postprandial-glucose-and-insulin-responses-in-humans
#9
Lotte Smolders, Ronald P Mensink, Mark V Boekschoten, Rogier J J de Ridder, Jogchum Plat
BACKGROUND & AIMS: Chocolate consumption is associated with a decreased risk for CVD. Theobromine, a compound in cocoa, may explain these effects as it favorably affected fasting serum lipids. However, long-term effects of theobromine on postprandial metabolism as well as underlying mechanisms have never been studied. The objective was to evaluate the effects of 4-week theobromine consumption (500 mg/day) on fasting and postprandial lipid, lipoprotein and glucose metabolism, and duodenal gene expression...
June 10, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28644867/host-derived-apolipoproteins-play-comparable-roles-with-viral-secretory-proteins-erns-and-ns1-in-the-infectious-particle-formation-of-flaviviridae
#10
Takasuke Fukuhara, Tomokazu Tamura, Chikako Ono, Mai Shiokawa, Hiroyuki Mori, Kentaro Uemura, Satomi Yamamoto, Takeshi Kurihara, Toru Okamoto, Ryosuke Suzuki, Kentaro Yoshii, Takeshi Kurosu, Manabu Igarashi, Hiroshi Aoki, Yoshihiro Sakoda, Yoshiharu Matsuura
Amphipathic α-helices of exchangeable apolipoproteins have shown to play crucial roles in the formation of infectious hepatitis C virus (HCV) particles through the interaction with viral particles. Among the Flaviviridae members, pestivirus and flavivirus possess a viral structural protein Erns or a non-structural protein 1 (NS1) as secretory glycoproteins, respectively, while Hepacivirus including HCV has no secretory glycoprotein. In case of pestivirus replication, the C-terminal long amphipathic α-helices of Erns are important for anchoring to viral membrane...
June 23, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28644829/swapping-the-n-and-c-terminal-domains-of-human-apolipoprotein-e3-and-ai-reveals-insights-into-their-structure-activity-relationship
#11
Mark T Lek, Siobanth Cruz, Nnejiuwa U Ibe, Wendy H J Beck, John K Bielicki, Paul M M Weers, Vasanthy Narayanaswami
Apolipoprotein (apo) E3 and apoAI are exchangeable apolipoproteins that play a dominant role in regulating plasma lipoprotein metabolism. ApoE3 (299 residues) is composed of an N-terminal (NT) domain bearing a 4-helix bundle and a C-terminal (CT) domain bearing a series of amphipathic α-helices. ApoAI (243 residues) also comprises a highly helical NT domain and a less structured CT tail. The objective of this study was to understand their structural and functional role by generating domain swapped chimeras: apoE3-NT/apoAI-CT and apoAI-NT/apoE-CT...
2017: PloS One
https://www.readbyqxmd.com/read/28641921/genome-wide-association-and-interaction-studies-of-csf-t-tau-a%C3%AE-42-ratio-in-adni-cohort
#12
Jin Li, Qiushi Zhang, Feng Chen, Xianglian Meng, Wenjie Liu, Dandan Chen, Jingwen Yan, Sungeun Kim, Lei Wang, Weixing Feng, Andrew J Saykin, Hong Liang, Li Shen
The pathogenic relevance in Alzheimer's disease (AD) presents a decrease of cerebrospinal fluid amyloid-ß42 (Aß42) burden and an increase in cerebrospinal fluid total tau (T-tau) levels. In this work, we performed genome-wide association study (GWAS) and genome-wide interaction study of T-tau/Aß42 ratio as an AD imaging quantitative trait on 843 subjects and 563,980 single-nucleotide polymorphisms (SNPs) in ADNI cohort. We aim to identify not only SNPs with significant main effects but also SNPs with interaction effects to help explain "missing heritability"...
May 15, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28640987/independent-effects-of-apolipoprotein-e-and-cerebrovascular-burden-on-later-life-depression-the-wisconsin-longitudinal-study
#13
Rosanna G Scott, Daniel L Paulson
OBJECTIVE: Studies evaluating the effect of apolipoprotein E (APOE) on vascular depression are sparse, employ heterogeneous methods, and yield inconsistent results. One possibility is that APOE is a moderator of another predictor such as cerebrovascular burden. This longitudinal study examines the relationships between APOE, cerebrovascular burden, and depressive symptomatology in a large cohort sample from midlife to later life. METHODS: Data include 3,203 participants across 18 years (1993-2011) from the Wisconsin Longitudinal Study (baseline mean age = 53 years)...
June 20, 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28637178/the-at04a-vaccine-against-proprotein-convertase-subtilisin-kexin-type-9-reduces-total-cholesterol-vascular-inflammation-and-atherosclerosis-in-apoe-3leiden-cetp-mice
#14
Christine Landlinger, Marianne G Pouwer, Claudia Juno, José W A van der Hoorn, Elsbet J Pieterman, J Wouter Jukema, Guenther Staffler, Hans M G Princen, Gergana Galabova
Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target for the treatment of hypercholesterolaemia and atherosclerosis. PCSK9 binds to the low density lipoprotein receptor and enhances its degradation, which leads to the reduced clearance of low density lipoprotein cholesterol (LDLc) and a higher risk of atherosclerosis. In this study, the AT04A anti-PCSK9 vaccine was evaluated for its therapeutic potential in ameliorating or even preventing coronary heart disease in the atherogenic APOE*3Leiden...
June 19, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28636914/peptide-protein-binding-investigated-by-far-ir-spectroscopy-and-molecular-dynamics-simulations
#15
Yoann Cote, Yves Nominé, Juan Ramirez, Petra Hellwig, Roland H Stote
Molecular dynamics (MD) simulations and far-infrared (far-IR) spectroscopy were combined to study peptide binding by the second PDZ domain (PDZ1) of MAGI1, which has been identified as an important target for the Human Papilloma Virus. PDZ1 recognizes and binds to the C-terminal end of the E6 protein from high-risk Human Papilloma Virus. The far-IR spectra of two forms of the protein, an unbound APO form and a HOLO form (where the PDZ1 is bound to an 11-residue peptide derived from the C terminus of HPV16 E6), were obtained...
June 20, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28634550/sortilin-related-receptor-expression-in-human-neural-stem-cells-derived-from-alzheimer-s-disease-patients-carrying-the-apoe-epsilon-4-allele
#16
Alen Zollo, Zoe Allen, Helle F Rasmussen, Filomena Iannuzzi, Yichen Shi, Agnete Larsen, Thorsten J Maier, Carmela Matrone
Alzheimer's disease (AD) is the most common form of dementia in the elderly; important risk factors are old age and inheritance of the apolipoprotein E4 (APOE4) allele. Changes in amyloid precursor protein (APP) binding, trafficking, and sorting may be important AD causative factors. Secretase-mediated APP cleavage produces neurotoxic amyloid-beta (Aβ) peptides, which form lethal deposits in the brain. In vivo and in vitro studies have implicated sortilin-related receptor (SORL1) as an important factor in APP trafficking and processing...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28634213/omega-3-fatty-acids-increase-the-unfolded-protein-response-and-improve-amyloid-%C3%AE-phagocytosis-by-macrophages-of-patients-with-mild-cognitive-impairment
#17
Henry M Olivera-Perez, Larry Lam, Johnny Dang, Weilan Jiang, Fabian Rodriguez, Elizabeth Rigali, Sarah Weitzman, Verna Porter, Liudmilla Rubi, Marco Morselli, Matteo Pellegrini, Milan Fiala
Mϕs of patients with Alzheimer's disease and mild cognitive impairment (MCI) are defective in amyloid-β1-42 (Aβ) phagocytosis and have low resistance to apoptosis by Aβ. ω-3 in vitro and in vivo and the ω-3 mediator, resolvin D1, in vitro increase Aβ phagocytosis by Mϕs of patients with MCI. We have investigated the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress by Mϕs in a longitudinal study of fish-derived, ω-3-supplemented patients with MCI. Patients in the apolipoprotein E (ApoE)e3/e3 subgroup over time exhibited an increase of protein kinase RNA-like ER kinase (PERK) expression, Aβ phagocytosis, intermediate M1-M2 Mϕ type, and a Mini-Mental State Examination (MMSE) rate of change of +1...
June 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28633142/multifactorial-analysis-of-a-biomarker-pool-for-alzheimer-disease-risk-in-a-north-indian-population
#18
Puneet Talwar, Sandeep Grover, Juhi Sinha, Puneet Chandna, Rachna Agarwal, Suman Kushwaha, Ritushree Kukreti
BACKGROUND: Alzheimer disease (AD) is a progressive neurodegenerative disease with a complex multifactorial etiology. Here, we aim to identify a biomarker pool comprised of genetic variants and blood biomarkers as predictor of AD risk. METHODS: We performed a case-control study involving 108 cases and 159 non-demented healthy controls to examine the association of multiple biomarkers with AD risk. RESULTS: The APOE genotyping revealed that ε4 allele frequency was significantly high (p value = 0...
June 21, 2017: Dementia and Geriatric Cognitive Disorders
https://www.readbyqxmd.com/read/28632940/characterization-of-the-i4399m-variant-of-apolipoprotein-a-implications-for-altered-prothrombotic-properties-of-lipoprotein-a
#19
Corey A Scipione, Jackson T McAiney, Daniel J Simard, Zainab A Bazzi, Matthew Gemin, Rocco Romagnuolo, Fraser L Macrae, Robert A Ariëns, Robert A Hegele, Janeen Auld, James W Gauld, Michael B Boffa, Marlys L Koschinsky
BACKGROUND: Lipoprotein(a) (Lp(a)) is a causal risk factor for a variety of cardiovascular diseases. Apolipoprotein(a) (apo(a)), the distinguishing component of Lp(a), is homologous to plasminogen, suggesting that Lp(a) can interfere with the normal fibrinolytic functions of plasminogen. This has implications for the persistence of fibrin clots in the vasculature and hence to atherothrombotic diseases. A single nucleotide polymorphism (rs3798220) in the gene encoding apo(a) has been reported that results in an Ile to Met substitution in the protease-like domain (I4399M variant)...
June 20, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28632844/complement-mediated-regulation-of-apolipoprotein-e-in-cultured-human-rpe-cells
#20
Ping Yang, Nikolai P Skiba, Grace M Tewkesbury, Victoria M Treboschi, Peter Baciu, Glenn J Jaffe
PURPOSE: Complement activation is implicated in the pathogenesis of age-related macular degeneration (AMD). Apolipoprotein E (ApoE) and complement activation products such as membrane attack complex (MAC) are present in eyes of individuals with AMD. Herein, we investigated the effect of complement activation on induction of ApoE accumulation in human retinal pigment epithelial (RPE) cells. METHODS: Cultured human RPE cells were primed with a complement-fixing antibody followed by treatment with C1q-depleted (C1q-Dep) human serum to elicit alternative pathway complement activation...
June 1, 2017: Investigative Ophthalmology & Visual Science
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