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Shu-Jian Wei, Lin Cheng, Er-Shun Liang, Qi Wang, Sheng-Nan Zhou, Hao Xu, Long-Hua Hui, Zhi-Ming Ge, Ming-Xiang Zhang
Poly (ADP-ribose) polymerase (PARP) plays an important role in endothelial dysfunction, leading to atherogenesis and vascular-related diseases. However, whether PARP regulates nitric oxide (NO), a key regulator of endothelial function, is unclear so far. We investigated whether inhibition of PARP-1, the most abundant PARP isoform, prevents atherogenesis by regulating NO production and tried to elucidate the possible mechanisms involved in this phenomenon. In apolipoprotein E-deficient (apoE(-/-) ) mice fed a high-cholesterol diet for 12 weeks, PARP-1 inhibition via treatment with 3,4-dihydro-54-(1-piperindinyl) butoxy-1(2H)-isoquinoline (DPQ) or PARP-1 gene knockoutreduced aortic atherosclerotic plaque areas (49% and 46%, respectively)...
October 18, 2016: Clinical and Experimental Pharmacology & Physiology
Ingmar Skoog, Helena Hörder, Kerstin Frändin, Lena Johansson, Svante Östling, Kaj Blennow, Henrik Zetterberg, Anna Zettergren
The association between decline in physical function and age-related conditions, such as reduced cognitive performance and vascular disease, may be explained by genetic influence on shared biological pathways of importance for aging. The apolipoprotein E (APOE) gene is well-known for its association with Alzheimer's disease, but has also been related to other disorders of importance for aging. The aim of this study was to investigate possible associations between APOE allele status and physical function in a population-based longitudinal study of older individuals...
2016: Frontiers in Aging Neuroscience
Karina Di Gregoli, Nur Najmi Mohamad Anuar, Rosaria Bianco, Stephen J White, Andrew C Newby, Sarah J George, Jason L Johnson
RATIONALE: Atherosclerosis and aneurysms are leading causes of mortality worldwide. MicroRNAs (miRs) are key determinants of gene and protein expression, and atypical miR expression has been associated with a number of cardiovascular diseases; although their contributory role to atherosclerotic plaque and abdominal aortic aneurysm (AAA) stability are poorly understood. OBJECTIVE: To investigate whether miR-181b regulates TIMP-3 expression and affects atherosclerosis and aneurysms Methods and Results: Here, we demonstrate that miR-181b was over-expressed in symptomatic human atherosclerotic plaques and abdominal aortic aneurysms, and correlated with decreased expression of predicted miR-181b targets, TIMP-3 and elastin...
October 18, 2016: Circulation Research
Li Qun, Xi Wenda, Sun Weihong, Ma Jianyang, Cai Wei, Lou Fangzhou, Xu Zhenyao, Gao Pingjin
BACKGROUND AND AIMS: The CCL20/CCR6 axis has been shown to play a vital role in the pathogenesis of atherosclerosis (AS). However, the regulatory mechanism remains unclear. Here, we studied the miRNA-mediated epigenetic regulation of the CCL20/CCR6 axis in atherogenesis. METHODS: CCR6(+/+)ApoE-/- and CCR6(-/-)ApoE-/- mice were fed a high-fat diet for 24 weeks. Plaque size was evaluated via ultrasound biomicroscope and hematoxylin and eosin. Protein expression were measured by Western blotting or immunofluorescence/immunohistochemistry or ELISA, and gene mRNA levels were detected by RT-PCR...
October 8, 2016: Atherosclerosis
Carrie J Finno, Matthew H Bordbari, Stephanie J Valberg, David Lee, Josi Herron, Kelly Hines, Tamer Monsour, Erica Scott, Danika L Bannasch, James Mickelson, Libin Xu
Specific spontaneous heritable neurodegenerative diseases have been associated with lower serum and cerebrospinal fluid α-tocopherol (α-TOH) concentrations. Equine neuroaxonal dystrophy (eNAD) has similar histologic lesions to human ataxia with vitamin E deficiency caused by mutations in the α-TOH transfer protein gene (TTPA). Mutations in TTPA are not present with eNAD and the molecular basis remains unknown. Given the neuropathologic phenotypic similarity of the conditions, we assessed the molecular basis of eNAD by global transcriptome sequencing of the cervical spinal cord...
October 14, 2016: Free Radical Biology & Medicine
Akira Takashima, Daiju Fukuda, Kimie Tanaka, Yasutomi Higashikuni, Yoichiro Hirata, Sachiko Nishimoto, Shusuke Yagi, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Yutaka Taketani, Michio Shimabukuro, Masataka Sata
BACKGROUND AND AIMS: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are major components of n-3 polyunsaturated fatty acids (n-3 PUFAs) which inhibit atherogenesis, although few studies have examined the effects of the combination of EPA and DHA on atherogenesis. The aim of this study was to investigate whether DHA has additional anti-atherosclerotic effects when combined with EPA. METHODS: Male 8-week-old apolipoprotein E-deficient (Apoe(-/-)) mice were fed a western-type diet supplemented with different amounts of EPA and DHA; EPA (2...
October 5, 2016: Atherosclerosis
Isabel López, Estela Sangüesa, Yves Vancraenendonck, Estefanía Zuriaga, María Pilar Ribate, Cristina Belén García
Vitamin K antagonists are highly effective antithrombotic drugs. However, appropriate dosing is difficult to establish owing to its narrow therapeutic window as well as widespread inter- and intra-individual variability in dosage. Compared with dosing solely based on clinical information, pharmacogenetics can help improve the therapy with coumarins by decreasing the time to reach a stable dose and reducing the risk of bleeding. Most of the studies about genotyping of patients using vitamin K antagonists have focused on predicting the stable dose...
October 14, 2016: Drug Metabolism and Personalized Therapy
Andrew T Grainger, Michael B Jones, Jing Li, Mei-Hua Chen, Ani Manichaikul, Weibin Shi
BACKGROUND AND AIMS: Recent genome-wide association studies (GWAS) have identified over 50 significant loci containing common variants associated with coronary artery disease. However, these variants explain only 26% of the genetic heritability of the disease, suggesting that many more variants remain to be discovered. Here, we examined the genetic basis underlying the marked difference between SM/J-Apoe(-/-) and BALB/cJ-Apoe(-/-) mice in atherosclerotic lesion formation. METHODS: 206 female F2 mice generated from an intercross between the two Apoe(-/-) strains were fed 12 weeks of western diet...
October 6, 2016: Atherosclerosis
Line S Bisgaard, Christina K Mogensen, Alexander Rosendahl, Helena Cucak, Lars Bo Nielsen, Salka E Rasmussen, Tanja X Pedersen
Macrophages are heterogeneous and can polarize into specific subsets, e.g. pro-inflammatory M1-like and re-modelling M2-like macrophages. To determine if peritoneal macrophages (PEMs) or bone marrow derived macrophages (BMDMs) resembled aortic macrophages from ApoE-/- mice, their M1/M2 phenotype, inflammatory status, and lipid metabolism signatures were compared. oxLDL accumulation was similar in PEMs and BMDMs. On protein expression level, BMDMs showed an M2-like CD206(high)CD11c(low) profile, while cholesterol loading led to enhanced CD11c expression and reduced MCP-1 secretion...
October 13, 2016: Scientific Reports
Qing Ye, Fan Su, Hao Shu, Liang Gong, Chunming Xie, Zhijun Zhang, Feng Bai
Previous cross-sectional studies that investigated the effects of apolipoprotein E (ApoE) ε4 status on hippocampal networks have shown inconsistent results. Aging is a well-known risk factor for Alzheimer's disease (AD) and could strongly interact with ApoE-related vulnerabilities to affect AD risk. However, no longitudinal data have been published regarding the interaction of the ApoE genotype and aging on hippocampal networks. Fifty-one patients with amnestic-type mild cognitive impairment (aMCI) and 64 matched cognitively normal elderly subjects underwent resting-state fMRI scans and neuropsychological tests at baseline and at a 35-month follow-up...
October 12, 2016: Brain Imaging and Behavior
Susan J Pressler, Jordan M Harrison, Marita Titler, Todd M Koelling, Miyeon Jung, Susan G Dorsey, Giorgos Bakoyannis, Penny L Riley, Lisa Hoyland-Domenico, Bruno Giordani
Twenty-three percent to 50% of heart failure (HF) patients have memory loss. Objectives were to (a) characterize major allelic frequency of 2 variants in apolipoprotein (APOE) gene in HF patients, (b) evaluate differences in memory and serum brain-derived neurotrophic factor (BDNF) levels based on APOE ε4 allele(s), and (c) estimate effect sizes (ESs) and confidence intervals (CIs). In this pilot, 29 HF patients were enrolled and 26 completed. Recall and delayed recall memory were measured at baseline and 12 weeks...
October 12, 2016: Western Journal of Nursing Research
Tahir Bezgin, Cihangir Kaymaz, Özgür Akbal, Fatih Yılmaz, Hacer Ceren Tokgöz, Nihal Özdemir
BACKGROUND: Venous thromboembolism (VTE) is a common and potentially lethal disorder that manifests mainly as deep vein thrombosis (DVT) of the extremities or pulmonary embolism (PE) and occurs as a consequence of genetic and environmental risk factors. We aimed to assess the role of inherited thrombophilia as a causative or additive factor in the development of VTE. METHODS: The study included 310 patients (female: 154; mean age: 52.3 ± 16.9 years) with a first episode of VTE and 289 age- and sex-matched healthy controls...
October 11, 2016: Clinical and Applied Thrombosis/hemostasis
Nguyen Thi Hong Hanh, Bui Thi Nhung, Duong Thi Anh Dao, Le Thi Tuyet, Le Thi Hop, Tran Quang Binh, Vu Thi Minh Thuc
BACKGROUND: The dyslipidemia associated with obesity plays a major role in the development of atherosclerosis and cardiovascular disease. Dyslipidemia in childhood can progress in adult stage. APOE is one of the most important genes that regulate plasma lipid transport and clearance. The study aimed to assess whether the common APOE polymorphism is associated with lipid profiles and dyslipidemia, and it could be modulated by obesity-related traits (body mass index, waist circumference, hip circumference, and waist-to-hip ratio) in Vietnamese children...
October 10, 2016: Lipids in Health and Disease
Xiaoyue Pan, Christopher A Bradfield, M Mahmood Hussain
Circadian rhythms controlled by clock genes affect plasma lipids. Here we show that global ablation of Bmal1 in Apoe(-/-) and Ldlr(-/-) mice and its liver-specific ablation in Apoe(-/-) (L-Bmal1(-/-)Apoe(-/-)) mice increases, whereas overexpression of BMAL1 in L-Bmal1(-/-)Apoe(-/-) and Apoe(-/-)mice decreases hyperlipidaemia and atherosclerosis. Bmal1 deficiency augments hepatic lipoprotein secretion and diminishes cholesterol excretion to the bile. Further, Bmal1 deficiency reduces expression of Shp and Gata4...
October 10, 2016: Nature Communications
Gennady V Roshchupkin, Hieab H Adams, Sven J van der Lee, Meike W Vernooij, Cornelia M van Duijn, Andre G Uitterlinden, Aad van der Lugt, Albert Hofman, Wiro J Niessen, Mohammad A Ikram
The neural substrate of genetic risk variants for Alzheimer's disease (AD) remains unknown. We studied their effect on healthy brain morphology to provide insight into disease etiology in the preclinical phase. We included 4071 nondemented, elderly participants of the population-based Rotterdam Study who underwent brain magnetic resonance imaging and genotyping. We performed voxel-based morphometry (VBM) on all gray-matter voxels for 19 previously identified, common AD risk variants. Whole-brain expression data from the Allen Human Brain Atlas was used to examine spatial overlap between VBM association results and expression of genes in AD risk loci regions...
September 4, 2016: Neurobiology of Aging
Joanna Martenka, Krystyna Soszyńska
Apolipoprotein E is a transport protein, which by binding to lipids forms a lipoprotein particle. It is responsible for transport and redistribution of lipids between cells and tissues. Apolipoprotein E circulates in blood mainly as a component of VLDL (very low density lipoproteins) HDL (high density lipoproteins) chylomicrons and chylomicron remnants. It assists in the flow of cholesterol from peripheral cells to extracellular space. Apolipoprotein E is one of the most studied apolipoproteins. There are three isoforms of this protein: E2, E3 and E4...
2016: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
Fan Zhu, Bharat Panwar, Hiroko H Dodge, Hongdong Li, Benjamin M Hampstead, Roger L Albin, Henry L Paulson, Yuanfang Guan
We present COMPASS, a COmputational Model to Predict the development of Alzheimer's diSease Spectrum, to model Alzheimer's disease (AD) progression. This was the best-performing method in recent crowdsourcing benchmark study, DREAM Alzheimer's Disease Big Data challenge to predict changes in Mini-Mental State Examination (MMSE) scores over 24-months using standardized data. In the present study, we conducted three additional analyses beyond the DREAM challenge question to improve the clinical contribution of our approach, including: (1) adding pre-validated baseline cognitive composite scores of ADNI-MEM and ADNI-EF, (2) identifying subjects with significant declines in MMSE scores, and (3) incorporating SNPs of top 10 genes connected to APOE identified from functional-relationship network...
October 5, 2016: Scientific Reports
Rinku Pal, Qingen Ke, German A Pihan, Ayce Yesilaltay, Marsha L Penman, Li Wang, Chandramohan Chitraju, Peter M Kang, Monty Krieger, Olivier Kocher
The HDL receptor SR-BI mediates the transfer of cholesteryl esters from HDL to cells and controls HDL abundance and structure. Depending on the genetic background, loss of SR-BI causes hypercholesterolemia, anemia, reticulocytosis, splenomegaly, thrombocytopenia, female infertility and fatal coronary heart disease (CHD). The C-terminus of SR-BI (505QEAKL509) must bind to the cytoplasmic adaptor PDZK1 for normal hepatic -but not steroidogenic cell- expression of SR-BI protein. To determine if SR-BI's C-terminus is also required for normal protein levels in steroidogenic cells, we introduced into SR-BI's gene a 507Ala/STOP mutation that produces a truncated receptor (SR-BIΔCT)...
September 30, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Daniela Belletti, Francesca Pederzoli, Flavio Forni, Maria Angela Vandelli, Giovanni Tosi, Barbara Ruozi
INTRODUCTION: New frontiers in nanomedicine are moving towards the research of new biomaterials. Apoferritin (APO), is a uniform regular self-assemblies nano-sized protein with excellent biocompatibility and a unique structure that affords it the ability to stabilize small active molecules in its inner core. AREAS COVERED: APO can be loaded by applying a passive process (mainly used for ions and metals) or by a unique formulative approach based on disassemby/reassembly process...
September 30, 2016: Expert Opinion on Drug Delivery
Nelzo C Ereful, Li-Yu Liu, Eric Tsai, Shu-Min Kao, Shalabh Dixit, Ramil Mauleon, Katrina Malabanan, Michael Thomson, Antonio Laurena, David Lee, Ian Mackay, Andy Greenland, Wayne Powell, Hei Leung
BACKGROUND: Information on the effect of stress on the allele-specific expression (ASE) profile of rice hybrids is limited. More so, the association of allelically imbalanced genes to important traits is yet to be understood. Here we assessed allelic imbalance (AI) in the heterozygote state of rice under non- and water-stress treatments and determined association of asymmetrically expressed genes with grain yield (GY) under drought stress by in-silico co-localization analysis and selective genotyping...
December 2016: Rice
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