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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
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
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
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
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
Pierre Mandin, Sylvia Chareyre, Frédéric Barras
UNLABELLED: Fe-S clusters are cofactors conserved through all domains of life. Once assembled by dedicated ISC and/or SUF scaffolds, Fe-S clusters are conveyed to their apo-targets via A-type carrier proteins (ATCs). Escherichia coli possesses four such ATCs. ErpA is the only ATC essential under aerobiosis. Recent studies reported a possible regulation of the erpA mRNA by the small RNA (sRNA) RyhB, which controls the expression of many genes under iron starvation. Surprisingly, erpA has not been identified in recent transcriptomic analysis of the iron starvation response, thus bringing into question the actual physiological significance of the putative regulation of erpA by RyhB...
September 20, 2016: MBio
Ángela Rodríguez-Cárdenas, Adriana L Rojas, María Conde-Giménez, Adrián Velázquez-Campoy, Ramón Hurtado-Guerrero, Javier Sancho
Streptococcus pneumoniae (Sp) strain TIGR4 is a virulent, encapsulated serotype that causes bacteremia, otitis media, meningitis and pneumonia. Increased bacterial resistance and limited efficacy of the available vaccine to some serotypes complicate the treatment of diseases associated to this microorganism. Flavodoxins are bacterial proteins involved in several important metabolic pathways. The Sp flavodoxin (Spfld) gene was recently reported to be essential for the establishment of meningitis in a rat model, which makes SpFld a potential drug target...
2016: PloS One
Iwona Bojar, Magdalena Stasiak, Anna Cyniak-Magierska, Dorota Raczkiewicz, Andrzej Lewiński
BACKGROUND: The objective of the study was to analyze a potential association between cognitive functions and thyroid status in postmenopausal women with different polymorphisms of the apolipoprotein E gene (APOE). METHODS: The examined population included 402 postmenopausal women from south-eastern Poland. The evaluation of cognitive functions was made with the use of the diagnostic Central Nervous System-Vital Signs equipment (Polish version). Multiplex polymerase chain reactions were performed to assess APOE polymorphisms...
September 21, 2016: Dementia and Geriatric Cognitive Disorders
Amit Kumar, Pradeep Kumar, Manya Prasad, Shubham Misra, Awadh Kishor Pandit, Kamalesh Chakravarty
BACKGROUND: Previous studies examining the association of apolipoprotein E (APOE) gene polymorphism with the risk of ischemic stroke (IS) have yielded conflicting results. Therefore, we performed a meta-analysis to investigate the association between APOE ε4 gene polymorphism and risk of IS. SUMMARY: A literature search for genetic association studies published before May 30, 2015, was conducted in the PubMed, EMBASE and Google Scholar databases. The following search terms were used: (apolipoprotein E) or (APOE) and (ε4) and (polymorphism) or (polymorphisms) and ('ischemic stroke' or 'IS') and ('cerebral infarction' or 'CI') and ('genetic polymorphism' or 'single nucleotide polymorphisms' or 'SNP')...
July 2016: Annals of Neurosciences
Peifen Chang, Xin Li, Chao Ma, Sisi Zhang, Zhen Liu, Kewei Chen, Lin Ai, Jingling Chang, Zhanjun Zhang
Polymorphisms of the apolipoprotein E (APOE) promoter rs405509 are related to Alzheimer's disease (AD). The T/T allele of rs405509 decreases the transcription of the APOE gene and leads to impairments in a specific brain structural network in aged individuals; thus, it is an important risk factor for AD. However, it remains unknown whether rs405509 affects white matter networks during aging. Here, we investigated the effect of the rs405509 genotype (T/T versus G-allele) on age-related brain white matter structural networks via construction of the graph theory-based structural connectome using diffusion MRI data in a large cohort...
September 13, 2016: Journal of Alzheimer's Disease: JAD
Christopher Konialis, Konstantinos Spengos, Panagiotis Iliopoulos, Sophia Karapanou, Elias Gialafos, Birgitta Hagnefelt, Konstantinos Vemmos, Nikolaos Zakopoulos, Constantinos Pangalos
BACKGROUND: Although several studies in various countries have indicated that the presence of the E4 allele of the apolipoprotein-E (APOE) gene is a risk factor for ischemic cerebrovascular disease, the strength of this association still remains a matter of debate. OBJECTIVES: The aim of the study was to determine the frequency of the APOE E4 allele and various other gene polymorphisms in in a well-characterized sample of Greek patients and to evaluate the potential associations with the risk of ischemic stroke (IS) and coronary heart disease (CHD)...
May 2016: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Karin Fehsel, Tamara Schikowski, Michaela Jänner, Anke Hüls, Mohammed Voussoughi, Thomas Schulte, Andrea Vierkötter, Tom Teichert, Christian Herder, Dorothea Sugiri, Ursula Krämer, Christian Luckhaus
Genetic and environmental risk factors contribute to the pathogenesis of Alzheimer's dementia. Besides known genetic risk factors like the apolipoprotein (APO) Eε4 allele, single nuclear polymorphisms (SNPs) of the estrogen receptors (ESRs) are candidate genetic risk factors, while air pollution represents an environmental risk factor for dementia. Effects of these risk factors and their interaction were investigated in the SALIA cohort of 834 non-demented elderly women. Cognitive function was assessed by the CERAD-plus test battery...
September 14, 2016: Journal of Neural Transmission
Farima Zahedi, Maliheh Nazari-Jahantigh, Zhe Zhou, Pallavi Subramanian, Yuanyuan Wei, Jochen Grommes, Stefan Offermanns, Sabine Steffens, Christian Weber, Andreas Schober
MicroRNAs (miRNAs) coordinate vascular repair by regulating injury-induced gene expression in vascular smooth muscle cells (SMCs) and promote the transition of SMCs from a contractile to a proliferating phenotype. However, the effect of miRNA expression in SMCs on neointima formation is unclear. Therefore, we studied the role of miRNA biogenesis by Dicer in SMCs in vascular repair. Following wire-induced injury to carotid arteries of Apolipoprotein E knockout (Apoe (-/-)) mice, miRNA microarray analysis revealed that the most significantly regulated miRNAs, such as miR-222 and miR-21-3p, were upregulated...
September 12, 2016: Cellular and Molecular Life Sciences: CMLS
Jianjia Fan, Shahab Zareyan, Wenchen Zhao, Yoko Shimizu, Tom A Pfeifer, Jun-Hyung Tak, Murray B Isman, Bernard Van den Hoven, Mark E Duggan, Michael W Wood, Cheryl L Wellington, Iva Kulic
The apolipoprotein E (APOE) gene is the most highly associated susceptibility locus for late onset Alzheimer's Disease (AD), and augmenting the beneficial physiological functions of apoE is a proposed therapeutic strategy. In a high throughput phenotypic screen for small molecules that enhance apoE secretion from human CCF-STTG1 astrocytoma cells, we show the chrysanthemic ester 82879 robustly increases expressed apoE up to 9.4-fold and secreted apoE up to 6-fold and is associated with increased total cholesterol in conditioned media...
2016: PloS One
Cristina Politi, Cinzia Ciccacci, Cinzia D'Amato, Giuseppe Novelli, Paola Borgiani, Vincenza Spallone
Diabetic polyneuropathy and cardiovascular autonomic neuropathy are common and disabling complications of diabetes. Although glycaemic control and cardiovascular risk factors are major contributory elements in its development, diabetic neuropathy recognizes a multifactorial influence and a multiplicity of pathogenetic mechanisms. Thus genetic and environmental factors may contribute to its susceptibility, each with a modest contribution, by targeting various metabolic and microvascular pathways whose alterations intervene in diabetic neuropathy pathogenesis...
October 2016: Diabetes Research and Clinical Practice
Ning Ding, Xin Wang, Marc G Weisskopf, David Sparrow, Joel Schwartz, Howard Hu, Sung Kyun Park
BACKGROUND: Cumulative exposure to lead is associated with cardiovascular outcomes. Polymorphisms in the δ-aminolevulinic acid dehydratase (ALAD), hemochromatosis (HFE), heme oxygenase-1 (HMOX1), vitamin D receptor (VDR), glutathione S-transferase (GST) supergene family (GSTP1, GSTT1, GSTM1), apolipoprotein E (APOE),angiotensin II receptor-1 (AGTR1) and angiotensinogen (AGT) genes, are believed to alter toxicokinetics and/or toxicodynamics of lead. OBJECTIVES: We assessed possible effect modification by genetic polymorphisms in ALAD, HFE, HMOX1, VDR, GSTP1, GSTT1, GSTM1, APOE, AGTR1 and AGT individually and as the genetic risk score (GRS) on the association between cumulative lead exposure and incident coronary heart disease (CHD) events...
2016: PloS One
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