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https://www.readbyqxmd.com/read/28442497/an-in-silico-model-of-retinal-cholesterol-dynamics-rcd-model-insights-into-the-pathophysiology-of-dry-age-related-macular-degeneration
#1
Seyedeh Maryam Zekavat, James Lu, Cyrille Maugeais, Norman A Mazer
We developed an in-silico mathematical model of retinal cholesterol (Ch) dynamics (RCD) to quantify the physiological rate of Ch turnover in the rod outer segment (ROS), the lipoprotein transport mechanisms by which Ch enters and leaves the outer retina, and the rates of drusen growth and macrophage-mediated clearance in dry Age-Related Macular Degeneration (AMD). Based on existing experimental data and mechanistic hypotheses, we estimate the Ch turnover rate in the ROS to be 1-6 pg/mm2/min, dependent on the rate of Ch recycling in the outer retina, and find comparable rates for LDL receptor-mediated endocytosis of Ch by the retinal pigment epithelium (RPE), ABCA1-mediated Ch transport from the RPE to outer retina, ABCA1-mediated Ch efflux from the RPE to choroid, and the secretion of 70 nm ApoB-Ch particles from the RPE...
April 25, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28437840/blood-biomarkers-of-carbohydrate-lipid-and-apolipoprotein-metabolisms-and-risk-of-amyotrophic-lateral-sclerosis-a-more-than-20-year-follow-up-of-the-swedish-amoris-cohort
#2
Daniela Mariosa, Niklas Hammar, Håkan Malmström, Caroline Ingre, Ingmar Jungner, Weimin Ye, Fang Fang, Göran Walldius
Objective To assess the associations of blood biomarkers of carbohydrate, lipid and apolipoprotein metabolisms with the future risk of ALS. Methods In the Apolipoprotein-related MOrtality RISk (AMORIS) study, we enrolled 636,132 men and women during 1985-1996 in Stockholm, Sweden with measurements of serum glucose, total cholesterol, triglycerides, apolipoprotein B (apoB), and apolipoprotein A-I (apoA-I). Serum LDL-C and HDL-C were either directly measured or calculated from total cholesterol, triglycerides and apoA-I...
April 24, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28434480/how-to-assess-and-manage-cardiovascular-risk-associated-with-lipid-alterations-beyond-ldl
#3
Maurizio Averna, Erik Stroes
BACKGROUND AND AIMS: The maintenance of clinically recommended levels of low-density lipoprotein cholesterol (LDL-C) through a statin therapy is a gold standard in the management of patients with dyslipidaemia and cardiovascular disease (CVD). However, even when LDL-C levels are at or below clinically recommended target levels, residual cardiovascular (CV) risk still remains. Therefore, assessing lipoproteins beyond LDL-C in managing CV risk is imperative. METHODS: A working group of clinical experts have assessed the role of lipoproteins other than LDL-C in identifying the CV risk in patients with dyslipidaemia and CVD and in the management of atherogenic dyslipidaemia associated with a number of other diseases...
April 2017: Atherosclerosis. Supplements
https://www.readbyqxmd.com/read/28432661/lipid-biomarkers-for-risk-assessment-in-acute-coronary-syndromes
#4
REVIEW
Jeffrey W Meeusen, Leslie J Donato, Allan S Jaffe
PURPOSE OF REVIEW: The objective of this review was to summarize evidence gathered for the prognostic value of routine and novel blood lipids and lipoproteins measured in patients with acute coronary syndromes (ACS). RECENT FINDINGS: Data supports clear association with risk and actionable value for non-high-density lipoprotein (Non-HDL) cholesterol and plasma ceramides in a setting of ACS. The prognostic value and clinical actionability of apolipoprotein B (apoB) and lipoprotein(a) [Lp(a)] in ACS have not been thoroughly tested, while the data for omega-3 fatty acids and oxidized low-density lipoprotein (Ox-LDL) are either untested or more varied...
June 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28431976/the-impact-of-exposure-to-environmental-contaminant-on-hepatocellular-lipid-metabolism
#5
Zongguang Hui, Rujiang Li, Li Chen
Increasing evidences show that ubiquitous perfluorooctanoic acid (PFOA), a representative environmental pollutant, is found to be linked to lipid dysmetabolism. However, the biological mechanism behind this outcome remains uninvestigated. In the present study, we established the PFOA-injured liver in mice to explore the underlying mechanism associated with PFOA-induced lipid disturbance in the liver via a group of biochemical and molecular assays. As results, PFOA-exposed mice showed increased transaminase (ALT), reduced triglyceride and free fatty acid contents in serum, as well as elevated level of hepatic triglyceride...
April 18, 2017: Gene
https://www.readbyqxmd.com/read/28431867/whole-exome-sequencing-identification-of-novel-candidate-genes-in-patients-with-proliferative-diabetic-retinopathy
#6
Cindy Ung, Angie V Sanchez, Lishuang Shen, Samaneh Davoudi, Tina Ahmadi, Daniel Navarro-Gomez, Ching J Chen, Heather Hancock, Alan Penman, Suzanne Hoadley, Mark Consugar, Carlos Restrepo, Vinay A Shah, Joseph F Arboleda-Velasquez, Lucia Sobrin, Xiaowu Gai, Leo A Kim
Rare or novel gene variants in patients with proliferative diabetic retinopathy may contribute to disease development. We performed whole exome sequencing (WES) on patients at the phenotypic extremes of diabetic retinal complications: 57 patients diagnosed with proliferativediabetic retinopathy (PDR) as cases and 13 patients with no diabetic retinopathy despite at least 10 years of type 2 diabetes as controls. Thirty-one out of the 57 cases and all 13 controls were from the African American Proliferative Diabetic Retinopathy Study (AA)...
April 18, 2017: Vision Research
https://www.readbyqxmd.com/read/28431663/effects-of-torcetrapib-and-statin-treatment-on-apoc-iii-and-apoprotein-defined-lipoprotein-subclasses-from-the-illuminate-trial
#7
John Bagdade, Philip Barter, Carmen Quiroga, Pierre Alaupovic
In the ILLUMINATE Trial, treatment with the cholesteryl ester transfer protein inhibitor torcetrapib resulted in a significant increase in both atherosclerotic cardiovascular disease events and total mortality which was not explained by changes in the routinely measured plasma lipids. To determine whether alterations in lipoproteins defined by their apoprotein content that are not estimated with conventional laboratory methods contributed to these unexpected events, we measured the apoB- and apoA-containing subclasses in a subgroup of ILLUMINATE participants...
March 18, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28430632/association-analysis-of-apo-gene-polymorphisms-with-ischemic-stroke-risk-a-case-control-study-in-a-chinese-han-population
#8
Rongjun Xiao, Shuaiqi Sun, Jiayi Zhang, Yongri Ouyang, Ning Zhang, Min Yang, Tianbo Jin, Ying Xia
This study aimed to assess the association of APO gene polymorphisms and ischemic stroke risk in a Chinese Han population. In this case-control study, we geno-typed 14 single nucleotide polymorphisms (SNPs) in 3 APO genes in 488 cases and 503 controls using Sequenom Mass-ARRAY technology and evaluated their association with ischemic stroke using the χ2 and genetic model analysis. In the allelic model analysis, we determined three SNPs were significantly associated with ischemic stroke: rs693 with a p value of 0...
February 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28428482/triglyceride-rich-lipoprotein-lpl-vldl-receptor-and-lp-a-vldl-receptor-pathways-for-macrophage-foam-cell-formation
#9
Sadao Takahashi
Very low-density lipoprotein (VLDL) receptor is a member of the low-density lipoprotein (LDL) receptor family. It binds triglyceride rich lipoprotein (TGRL) but not LDL, because it recognizes apolipoprotein (apo)E only but not apoB. The VLDL receptor functions as a peripheral lipoprotein receptor in concert with lipoprotein lipase (LPL) in heart, muscle, adipose tissue and macrophages. In contrast to the LDL receptor, VLDL receptor binds apo E2/2 VLDL and apoE3/3 VLDL particles, and its expression is not down-regulated by intracellular lipoproteins...
April 19, 2017: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/28428224/familial-hypercholesterolemia-and-type-2-diabetes-in-the-old-order-amish
#10
Huichun Xu, Kathleen A Ryan, Thomas J Jaworek, Lorraine Southam, Jeffrey G Reid, John D Overton, Aris Baras, Marja K Puurunen, Eleftheria Zeggini, Simeon I Taylor, Alan R Shuldiner, Braxton D Mitchell
Alleles associated with lower levels of low density lipoprotein cholesterol (LDL-C) have recently been associated with an increased risk of type 2 diabetes (T2D), highlighting the complex relationship between LDL-C and diabetes. This observation begs the question whether LDL-C-raising alleles are associated with a decreased risk of T2D. This issue was recently addressed in a large familial hypercholesterolemia (FH) screening study, which reported a lower prevalence of self-reported diabetes in FH subjects than age-matched relatives without FH...
April 20, 2017: Diabetes
https://www.readbyqxmd.com/read/28424539/%C3%AE-3-adrenoceptor-activation-upregulates-apolipoprotein-a-i-expression-in-hepg2-cells-which-might-further-promote-cholesterol-efflux-from-macrophage-foam-cells
#11
Xia-Qing Gao, Yan-Fang Li, Zhi-Li Jiang
OBJECTIVE: The aim of this study was to explore the effects of β3-adrenoceptor (β3-AR) activation on HepG2 cells and its influence on cholesterol efflux from macrophage foam cells. MATERIALS AND METHODS: HepG2 cells were cultured and treated with the β3-AR agonist, BRL37344, and antagonist, SR52390A, and the expression of apolipoprotein (Apo) A-I, ApoA-II, ApoB, and β3-AR in the supernatants and cells was determined. The expression of peroxisome proliferator-activated receptor (PPAR) γ and PPARα in the HepG2 cells was also assessed...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28419892/plasma-apolipoproteins-and-physical-and-cognitive-health-in-very-old-individuals
#12
Julia Muenchhoff, Fei Song, Anne Poljak, John D Crawford, Karen A Mather, Nicole A Kochan, Zixuan Yang, Julian N Trollor, Simone Reppermund, Kate Maston, Adam Theobald, Susanne Kirchner-Adelhardt, John B Kwok, Robyn L Richmond, Mark McEvoy, John Attia, Peter W Schofield, Henry Brodaty, Perminder S Sachdev
Apolipoproteins play a crucial role in lipid metabolism with implications in cardiovascular disease, obesity, diabetes, Alzheimer's disease, and longevity. We quantified 7 apolipoproteins in plasma in 1067 individuals aged 56-105 using immunoassays and explored relationships with APOE polymorphism ε2/3/4, vascular health, frailty, and cognition. ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH, and ApoJ decreased from mid-life, although ApoE and ApoJ had U-shaped trends. Centenarians had the highest ApoE levels and the lowest frequency of APOE ε4 allele relative to younger groups...
March 1, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28413474/obesity-contributes-more-to-increasing-apob-apoa1-ratio-than-hyperandrogenism-in-pcos-women-aged-20-38-years-in-china
#13
Jianhua Zheng, Qianqian Yin, Juanyi Cao, Bei Zhang
We investigated the association between the apolipoprotein B (ApoB)/apolipoprotein A1 (ApoA1) ratio and insulin resistance (IR), metabolic syndrome (MS) and its components in Chinese polycystic ovary syndrome (PCOS) adults. We also examined whether hyperandrogenism is involved in obesity-related metabolic abnormalities in a cohort of patients. A clinical cross-sectional study consisting of 532 Chinese PCOS adults aged 20-38 years was designed. Each subject underwent a physical examination and laboratory evaluation...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28412650/comparative-effects-of-cholesteryl-ester-transfer-protein-inhibition-statin-or-ezetimibe-on-lipid-factors-the-accentuate-trial
#14
Stephen J Nicholls, Kausik K Ray, Christie M Ballantyne, Lauren A Beacham, Debra L Miller, Giacomo Ruotolo, Steven E Nissen, Jeffrey S Riesmeyer
BACKGROUND AND AIMS: The optimal approaches to management of patients treated with moderate statin doses on lipid parameters are unknown. The ACCENTUATE study aimed to compare the effects of adding the cholesteryl ester transfer protein inhibitor (CETP) evacetrapib, ezetimibe or increasing statin dose in atorvastatin-treated high-vascular risk patients on lipid parameters. METHODS: 366 patients with atherosclerotic cardiovascular disease (ASCVD) and/or diabetes were treated with atorvastatin 40 mg/day for 28 days prior to randomization to atorvastatin 40 mg plus evacetrapib 130 mg, atorvastatin 80 mg, atorvastatin 40 mg plus ezetimibe 10 mg or atorvastatin 40 mg plus placebo, daily for 90 days at 64 centers in the United States...
April 8, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28411432/automated-in-line-mixing-system-for-large-scale-production-of-chitosan-based-polyplexes
#15
Ashkan Tavakoli Naeini, Ousamah Younoss Soliman, Mohamad Gabriel Alameh, Marc Lavertu, Michael D Buschmann
Chitosan (CS)-based polyplexes are efficient non-viral gene delivery systems that are most commonly prepared by manual mixing. However, manual mixing is not only poorly controlled but also restricted to relatively small preparation volumes, limiting clinical applications. In order to overcome these drawbacks and to produce clinical quantities of CS-based polyplexes, a fully automated in-line mixing platform was developed for production of large batches of small-size and homogeneous CS-based polyplexes. Operational conditions to produce small-sized homogeneous polyplexes were identified...
April 7, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28406212/human-knockouts-and-phenotypic-analysis-in-a-cohort-with-a-high-rate-of-consanguinity
#16
Danish Saleheen, Pradeep Natarajan, Irina M Armean, Wei Zhao, Asif Rasheed, Sumeet A Khetarpal, Hong-Hee Won, Konrad J Karczewski, Anne H O'Donnell-Luria, Kaitlin E Samocha, Benjamin Weisburd, Namrata Gupta, Mozzam Zaidi, Maria Samuel, Atif Imran, Shahid Abbas, Faisal Majeed, Madiha Ishaq, Saba Akhtar, Kevin Trindade, Megan Mucksavage, Nadeem Qamar, Khan Shah Zaman, Zia Yaqoob, Tahir Saghir, Syed Nadeem Hasan Rizvi, Anis Memon, Nadeem Hayyat Mallick, Mohammad Ishaq, Syed Zahed Rasheed, Fazal-Ur-Rehman Memon, Khalid Mahmood, Naveeduddin Ahmed, Ron Do, Ronald M Krauss, Daniel G MacArthur, Stacey Gabriel, Eric S Lander, Mark J Daly, Philippe Frossard, John Danesh, Daniel J Rader, Sekar Kathiresan
A major goal of biomedicine is to understand the function of every gene in the human genome. Loss-of-function mutations can disrupt both copies of a given gene in humans and phenotypic analysis of such 'human knockouts' can provide insight into gene function. Consanguineous unions are more likely to result in offspring carrying homozygous loss-of-function mutations. In Pakistan, consanguinity rates are notably high. Here we sequence the protein-coding regions of 10,503 adult participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS), designed to understand the determinants of cardiometabolic diseases in individuals from South Asia...
April 12, 2017: Nature
https://www.readbyqxmd.com/read/28405938/genetic-architecture-of-familial-hypercholesterolaemia
#17
REVIEW
Mahtab Sharifi, Marta Futema, Devaki Nair, Steve E Humphries
PURPOSE OF REVIEW: Familial hypercholesterolaemia (FH) is an inherited disorder of low-density lipoprotein cholesterol (LDL-C) which is characterised by a raised cholesterol level from birth and a high risk of premature coronary heart disease. In this paper, we review the genetic basis of FH and its impact on the clinical presentation. RECENT FINDINGS: Mutations in any of three genes (LDLR, APOB and PCSK9) are known to cause autosomal dominant FH, but a mutation can be found in only ∼40% of patients with a clinical diagnosis of FH...
May 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28400268/genetic-evidence-supporting-the-taxonomic-separation-of-the-arabian-and-northwest-african-subspecies-of-the-desert-hedgehog-paraechinus-aethiopicus
#18
Louiza Derouiche, Paul Vercammen, Rachid Bouhadad, Carlos Fernandes
Traditional subspecies call attention to differences between geographic populations with research potential, but their value is often in need of revision. Genetic data can be useful for evaluating the taxonomic validity of historical species and subspecies designations or for identifying morphologically cryptic divergent lineages worthy of further in-depth taxonomic study. The desert hedgehog (Paraechinus aethiopicus) has a wide but fragmented distribution in arid and semi-arid habitats from the northwest to the northeast of Africa and southwestern Asia, and its taxonomy is still unclear...
April 8, 2017: Gene
https://www.readbyqxmd.com/read/28392500/metabolism-and-proteomics-of-large-and-small-dense-ldl-in-combined-hyperlipidemia-effects-of-rosuvastatin
#19
Nuntakorn Thongtang, Margaret R Diffenderfer, Esther M M Ooi, P Hugh R Barrett, Scott M Turner, Ngoc-Anh Le, W Virgil Brown, Ernst J Schaefer
Small dense LDL (sdLDL) has been reported to be more atherogenic than large buoyant LDL (lbLDL). We examined the metabolism and protein composition of sdLDL and lbLDL in six subjects with combined hyperlipidemia on placebo and rosuvastatin 40 mg/day. ApoB-100 kinetics in triglyceride rich lipoproteins (TRL), lbLDL (density [d] 1.019-1.044 g/ml), and sdLDL (d 1.044-1.063 g/ml) were determined in the fed state using stable isotope tracers, mass spectrometry, and compartmental modeling. Compared with placebo, rosuvastatin decreased LDL cholesterol and apoB-100 levels in TRL, lbLDL, and sdLDL by significantly increasing the fractional catabolic rate of apoB-100 (TRL +45%; lbLDL +131%; sdLDL +97%), without a change in production...
April 9, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28391908/apob-lipoproteins-and-dysfunctional-white-adipose-tissue-relation-to-risk-factors-for-type-2-diabetes-in-humans
#20
Valérie Lamantia, Simon Bissonnette, Hanny Wassef, Yannick Cyr, Alexis Baass, Robert Dufour, Rémi Rabasa-Lhoret, May Faraj
BACKGROUND: Elevated plasma apoB is an independent predictor of T2D; however, underlying mechanisms remain unclear. Chronic reduction in white adipose tissue (WAT) function promotes T2D. We reported that differentiation of preadipocytes and acute incubation of human WAT with LDL induce their dysfunction (decreased hydrolysis and storage of triglyceride-rich lipoproteins [TRL]). OBJECTIVE: To examine the hypothesis that the association of plasma apoB with T2D risk factors, hypertriglyceridemia (hyperTG), insulin resistance (IR), and hyperinsulinemia, was dependent on WAT dysfunction...
January 2017: Journal of Clinical Lipidology
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