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https://www.readbyqxmd.com/read/27884961/therapeutic-silencing-of-fat-specific-protein-27-improves-glycemic-control-in-mouse-models-of-obesity-and-insulin-resistance
#1
Cédric Langhi, Noemí Arias, Ananthi Rajamoorthi, Jeannine Basta, Richard G Lee, Ángel Baldán
Obesity is a component of the metabolic syndrome, mechanistically linked to diabetes, fatty liver disease, and cardiovascular disease. Proteins that regulate the metabolic fate of intracellular lipid droplets are potential therapeutic candidates to treat obesity and its related consequences. CIDEC (cell death-inducing DFFA-like effector C), also known in mice as Fsp27 (fat-specific protein 27), is a lipid droplet-associated protein that prevents lipid mobilization and promotes intracellular lipid storage. The consequences of complete loss of FSP27 on hepatic metabolism and on insulin resistance are controversial, as both healthy and deleterious lipodystrophic phenotypes have been reported in Fsp27-/- mice...
November 24, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27797643/modern-management-of-familial-hypercholesterolemia
#2
P Barton Duell, Ishwarlal Jialal
Familial hypercholesterolemia (FH) is a common genetic disorder that can manifest clinically as both the severe homozygous (HoFH) form that often presents in childhood and the commoner heterozygous (HeFH) form that is typically identified in adults. The majority of genetic causes are due to defects in low-density lipoprotein (LDL) receptor synthesis and action. Until recently, it was exceedingly difficult to achieve the goal of a 50% reduction in LDL-cholesterol or LDL-C < 70-100 in these patients. Established therapies include statins, niacin, bile-acid sequestrants, and ezetimibe in various combinations...
December 2016: Metabolic Syndrome and related Disorders
https://www.readbyqxmd.com/read/27785114/lipoprotein-apheresis-in-the-management-of-severe-hypercholesterolemia-and-of-elevation-of-lipoprotein-a-current-perspectives-and-patient-selection
#3
REVIEW
Ulrich Julius
This review reports the current situation with respect to therapeutic options (lifestyle and drugs) reducing the concentrations of atherogenic low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp[a]). Three lipoprotein apheresis (LA) principles have been realized: precipitation, filtration, and adsorption. Available LA methods are herein described in detail - major components, pumps, extracorporeal volume, treated volume, and anticoagulation. General features of all LA methods as well as pleotropic effects are elaborated...
2016: Medical Devices: Evidence and Research
https://www.readbyqxmd.com/read/27770802/the-emerging-role-of-apolipoprotein-c-iii-beyond-effects-on-triglyceride-metabolism
#4
REVIEW
Mengdie Luo, Daoquan Peng
Apolipoprotein C-III has been referred to as an important participant in the metabolism of triglyceride-rich lipoproteins, leading to hypertriglyceridemia and thereafter cardiovascular disease. Accumulating evidence indicates that apolipoprotein C-III is a multifaceted protein which not only regulates triglyceride metabolism, but also participates in the atherosclerotic lesion formation and several other pathological processes involved in atherosclerosis. Based on data from experiments and clinical trials, some novel therapies such as antisense technology emerge...
October 22, 2016: Lipids in Health and Disease
https://www.readbyqxmd.com/read/27766009/cardiac-manifestations-of-congenital-generalized-lipodystrophy
#5
Vani P Sanon, Yehuda Handelsman, Son V Pham, Robert Chilton
IN BRIEF Congenital lipodystrophy is a rare genetic disorder characterized by a near-complete absence of fat cells, hypoleptinemia leading to a voracious appetite, and marked insulin resistance. This article focuses on the known cardiovascular manifestations of patients with congenital lipodystrophy, including cardiomyopathy, cardiac arrhythmias, and accelerated atherosclerosis arising from a markedly deranged metabolic milieu. Future research that targets leptin deficiency (metreleptin) and apoC3 mRNA (antisense oligonucleotide) could open a window for potential pharmacological treatment of this challenging disorder...
October 2016: Clinical Diabetes: a Publication of the American Diabetes Association
https://www.readbyqxmd.com/read/27761705/emerging-therapeutic-options-for-lowering-of-lipoprotein-a-implications-for-prevention-of-cardiovascular-disease
#6
Michael B Boffa
PURPOSE OF REVIEW: Elevated plasma concentrations of lipoprotein(a) (Lp(a)) are an independent and causal risk factor for cardiovascular diseases including coronary artery disease, ischemic stroke, and calcific aortic valve stenosis. This review summarizes the rationale for Lp(a) lowering and surveys relevant clinical trial data using a variety of agents capable of lowering Lp(a). RECENT FINDINGS: Contemporary guidelines and recommendations outline populations of patients who should be screened for elevated Lp(a) and who might benefit from Lp(a) lowering...
December 2016: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/27755115/truths-and-controversies-concerning-the-role-of-mirnas-in-atherosclerosis-and-lipid-metabolism
#7
Ángel Baldán, Carlos Fernández-Hernando
PURPOSE OF REVIEW: Better tools are sorely needed for both the prevention and treatment of cardiovascular diseases, which account for more than one-third of the deaths in Western countries. MicroRNAs typically regulate the expression of several mRNAs involved in the same biological process. Therapeutic manipulation of miRNAs could restore the expression of multiple players within the same physiologic pathway, and ideally offer better curative outcomes than conventional approaches that target only one single player within the pathway...
December 2016: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/27753829/sy-03-2-pathophysiologic-significance-of-non-coding-rna-in-hypertension
#8
Stephen Harrap
Genetic discovery in blood pressure is generally referenced in relation to protein-coding genes, despite the fact that genes less than 2% of the genome. Recent exploration of the DNA sequences between genes, once called "junk" DNA, has revealed a wealth of transcripts for RNA species that do not encode protein. These non-coding RNAs (ncRNAs) have emerged as dynamic managers of the business of the genome, able to coordinate the expression of genes in time and space to achieve the complexities of normal development and growth...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27704139/pigmy-microrna-surveillance-cops-in-therapies-kingdom
#9
Utpal Bhadra, Pradipta Patra, Jagamohan Chhatai, Manika Pal-Bhadra
MicroRNAs (miRNAs) are well preserved in every animal. These pigmy sized non-coding RNAs (21-23 nt), scattered in genome, are responsible for micromanaging the versatile gene regulations. Involvement of miRNAs was surveillance cops in all human diseases including cardiovascular defects, tumor formation, reproductive pathways, and neurological and autoimmune disorders. The effective functional role of miRNA can be reduced by chemical entities of antisense oligonucleotides and versatile small molecules that support the views of novel therapy of different human diseases...
September 28, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27678436/ten-years-of-lipoprotein-apheresis-for-familial-hypercholesterolemia-in-malaysia-a-creative-approach-by-a-cardiologist-in-a-developing-country
#10
Kah Lin Khoo, Michael M Page, Yin Mei Liew, Joep C Defesche, Gerald F Watts
BACKGROUND: Familial hypercholesterolemia (FH) leads to premature coronary artery disease and aortic stenosis, with undertreated severe forms causing death at a young age. Lipoprotein apheresis (LA) is often required for lowering low-density lipoprotein cholesterol levels in severe FH. OBJECTIVES: The objective of this study was to present the first experiences with LA in Malaysia, between 2004 and 2014. METHODS: We retrospectively collected data from patient records to assess the effectiveness, adverse effects, patient quality of life, and costs associated with an LA service for genetically confirmed homozygous and heterozygous FH...
September 2016: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/27665230/antisense-oligonucleotides-targeting-apolipoprotein-a-in-people-with-raised-lipoprotein-a-two-randomised-double-blind-placebo-controlled-dose-ranging-trials
#11
Nicholas J Viney, Julian C van Capelleveen, Richard S Geary, Shuting Xia, Joseph A Tami, Rosie Z Yu, Santica M Marcovina, Steven G Hughes, Mark J Graham, Rosanne M Crooke, Stanley T Crooke, Joseph L Witztum, Erik S Stroes, Sotirios Tsimikas
BACKGROUND: Elevated lipoprotein(a) (Lp[a]) is a highly prevalent (around 20% of people) genetic risk factor for cardiovascular disease and calcific aortic valve stenosis, but no approved specific therapy exists to substantially lower Lp(a) concentrations. We aimed to assess the efficacy, safety, and tolerability of two unique antisense oligonucleotides designed to lower Lp(a) concentrations. METHODS: We did two randomised, double-blind, placebo-controlled trials...
November 5, 2016: Lancet
https://www.readbyqxmd.com/read/27642882/sy-03-2-pathophysiologic-significance-of-non-coding-rna-in-hypertension
#12
Stephen Harrap
Genetic discovery in blood pressure is generally referenced in relation to protein-coding genes, despite the fact that genes less than 2% of the genome. Recent exploration of the DNA sequences between genes, once called "junk" DNA, has revealed a wealth of transcripts for RNA species that do not encode protein. These non-coding RNAs (ncRNAs) have emerged as dynamic managers of the business of the genome, able to coordinate the expression of genes in time and space to achieve the complexities of normal development and growth...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27613744/why-is-apolipoprotein-ciii-emerging-as-a-novel-therapeutic-target-to-reduce-the-burden-of-cardiovascular-disease
#13
REVIEW
Marja-Riitta Taskinen, Jan Borén
ApoC-III was discovered almost 50 years ago, but for many years, it did not attract much attention. However, as epidemiological and Mendelian randomization studies have associated apoC-III with low levels of triglycerides and decreased incidence of cardiovascular disease (CVD), it has emerged as a novel and potentially powerful therapeutic approach to managing dyslipidemia and CVD risk. The atherogenicity of apoC-III has been attributed to both direct lipoprotein lipase-mediated mechanisms and indirect mechanisms, such as promoting secretion of triglyceride-rich lipoproteins (TRLs), provoking proinflammatory responses in vascular cells and impairing LPL-independent hepatic clearance of TRL remnants...
October 2016: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/27594927/dna-methylation-at-birth-within-the-promoter-of-anril-predicts-markers-of-cardiovascular-risk-at-9%C3%A2-years
#14
Robert Murray, Jennifer Bryant, Phil Titcombe, Sheila J Barton, Hazel Inskip, Nicholas C Harvey, Cyrus Cooper, Karen Lillycrop, Mark Hanson, Keith M Godfrey
AIMS: Antisense non-coding RNA in the INK4 locus (ANRIL) fixed genetic variants have consistently been linked with coronary heart disease (CHD) risk. We investigated relationships between perinatal ANRIL promoter DNA methylation and CHD risk markers in children aged 9 years. Genetic variants in the non-coding RNA ANRIL identify it as an important CHD risk locus. Increasing evidence suggests that the early life environment may act through epigenetic processes to influence later CHD risk markers such as increased arterial pulse wave velocity (PWV, a measure of arterial stiffness) blood pressure or heart rate...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27578117/pediatric-experience-with-mipomersen-as-adjunctive-therapy-for-homozygous-familial-hypercholesterolemia
#15
Frederick J Raal, Marjet J Braamskamp, Sheryl L Selvey, Charlotte H Sensinger, John J Kastelein
BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare, inherited condition resulting in severely elevated low-density lipoprotein cholesterol levels (LDL-C) leading to premature cardiovascular disease and, often, death. Mipomersen is an antisense oligonucleotide that inhibits apolipoprotein B (apo B) synthesis, lowering LDL-C levels. Mipomersen has demonstrated efficacy in adult HoFH patients, possibly providing a therapeutic option for pediatric patients. Study objectives were to summarize mipomersen efficacy and safety in the pediatric cohort of a phase 3 randomized controlled trial (RCT) and subsequent open-label extension study (OLE)...
July 2016: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/27574949/long-non-coding-rna-hoxc-as1-suppresses-ox-ldl-induced-cholesterol-accumulation-through-promoting-hoxc6-expression-in-thp-1-macrophages
#16
Chuan Huang, Yan-Wei Hu, Jing-Jing Zhao, Xin Ma, Yuan Zhang, Feng-Xia Guo, Chun-Min Kang, Jing-Bo Lu, Jian-Cheng Xiu, Yan-Hua Sha, Ji-Juan Gao, Yan-Chao Wang, Pan Li, Bang-Ming Xu, Lei Zheng, Qian Wang
Atherosclerosis is a common pathological basis of cardiovascular disease, which remains the leading cause of mortality. Long non-coding RNAs (lncRNAs) are newly studied non-protein-coding RNAs involved in gene regulation, but how lncRNAs exert regulatory effect on atherosclerosis remains unclear. In this study, we found that lncRNA HOXC cluster antisense RNA 1 (HOXC-AS1) and homeobox C6 (HOXC6) were downregulated in carotid atherosclerosis by performing microarray analysis. The results were verified in atherosclerotic plaques and normal arterial intima tissues by quantitative reverse transcription PCR and western blot analysis...
August 30, 2016: DNA and Cell Biology
https://www.readbyqxmd.com/read/27569277/nampt-regulates-senescence-proliferation-and-migration-of-endothelial-progenitor-cells-through-the-sirt1-as-lncrna-mir-22-sirt1-pathway
#17
Guang-Feng Ming, Kai Wu, Kai Hu, Yao Chen, Jian Xiao
The importance of endothelial progenitor cells (EPCs) in cardiovascular diseases has been demonstrated by numerous studies. Previous studies have shown that Nicotinamide phosphoribosyltransferase (NAMPT) plays a role in EPC development by regulating Sirtuin 1 (SIRT1), but the specific mechanism has not yet been elucidated. After stimulating EPCs with NAMPT, expression of SIRT1 and SIRT1 antisense long non-coding RNA (AS lncRNA) was upregulated. Upon transfection of an SIRT1 AS lncRNA overexpression vector into EPCs, SIRT1 expression was upregulated...
September 23, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27539542/circular-non-coding-rna-anril-modulates-ribosomal-rna-maturation-and-atherosclerosis-in-humans
#18
Lesca M Holdt, Anika Stahringer, Kristina Sass, Garwin Pichler, Nils A Kulak, Wolfgang Wilfert, Alexander Kohlmaier, Andreas Herbst, Bernd H Northoff, Alexandros Nicolaou, Gabor Gäbel, Frank Beutner, Markus Scholz, Joachim Thiery, Kiran Musunuru, Knut Krohn, Matthias Mann, Daniel Teupser
Circular RNAs (circRNAs) are broadly expressed in eukaryotic cells, but their molecular mechanism in human disease remains obscure. Here we show that circular antisense non-coding RNA in the INK4 locus (circANRIL), which is transcribed at a locus of atherosclerotic cardiovascular disease on chromosome 9p21, confers atheroprotection by controlling ribosomal RNA (rRNA) maturation and modulating pathways of atherogenesis. CircANRIL binds to pescadillo homologue 1 (PES1), an essential 60S-preribosomal assembly factor, thereby impairing exonuclease-mediated pre-rRNA processing and ribosome biogenesis in vascular smooth muscle cells and macrophages...
August 19, 2016: Nature Communications
https://www.readbyqxmd.com/read/27503944/long-non-coding-rnas-towards-precision-medicine-in-diabetic-kidney-disease
#19
REVIEW
Usha Panchapakesan, Carol Pollock
Diabetic kidney disease (DKD) is escalating and is the major cause of end stage kidney failure. There is increasing evidence to support the role of epigenetic factors and metabolic memory in linking the environmental and genetic causes of this disease. Although our understanding of this disease has improved, there has been no significant efficacious therapeutic translation in the last decade. Current sequencing technology has allowed interrogation of the human transcriptome. It is evident that although approximately 80% of the genome is transcribed, only 1-2% is read and coded into protein...
September 1, 2016: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27443326/targeting-apoc-iii-to-reduce-coronary-disease-risk
#20
REVIEW
Sumeet A Khetarpal, Arman Qamar, John S Millar, Daniel J Rader
Triglyceride-rich lipoproteins (TRLs) are causal contributors to the risk of developing coronary artery disease (CAD). Apolipoprotein C-III (apoC-III) is a component of TRLs that elevates plasma triglycerides (TGs) through delaying the lipolysis of TGs and the catabolism of TRL remnants. Recent human genetics approaches have shown that heterozygous loss-of-function mutations in APOC3, the gene encoding apoC-III, lower plasma TGs and protect from CAD. This observation has spawned new interest in therapeutic efforts to target apoC-III...
September 2016: Current Atherosclerosis Reports
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