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https://www.readbyqxmd.com/read/28209220/very-low-density-lipoprotein-associated-apolipoproteins-predict-cardiovascular-events-and-are-lowered-by-inhibition%C3%A2-of%C3%A2-apoc-iii
#1
Raimund Pechlaner, Sotirios Tsimikas, Xiaoke Yin, Peter Willeit, Ferheen Baig, Peter Santer, Friedrich Oberhollenzer, Georg Egger, Joseph L Witztum, Veronica J Alexander, Johann Willeit, Stefan Kiechl, Manuel Mayr
BACKGROUND: Routine apolipoprotein (apo) measurements for cardiovascular disease (CVD) are restricted to apoA-I and apoB. Here, the authors measured an unprecedented range of apolipoproteins in a prospective, population-based study and relate their plasma levels to risk of CVD. OBJECTIVES: This study sought to measure apolipoproteins directly by mass spectrometry and compare their associations with incident CVD and to obtain a system-level understanding of the correlations of apolipoproteins with the plasma lipidome and proteome...
February 21, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28192479/comparison-of-zebrafish-tmem88a-mutant-and-morpholino-knockdown-phenotypes
#2
Alexander M J Eve, Elsie S Place, James C Smith
Tmem88a is a transmembrane protein that is thought to be a negative regulator of the Wnt signalling pathway. Several groups have used antisense morpholino oligonucleotides in an effort to characterise the role of tmem88a in zebrafish cardiovascular development, but they have not obtained consistent results. Here, we generate an 8 bp deletion in the coding region of the tmem88a locus using TALENs, and we have gone on to establish a viable homozygous tmem88aΔ8 mutant line. Although tmem88aΔ8 mutants have reduced expression of some key haematopoietic genes, differentiation of erythrocytes and neutrophils is unaffected, contradicting our previous study using antisense morpholino oligonucleotides...
2017: PloS One
https://www.readbyqxmd.com/read/28185213/hyperlipoproteinaemia-a-apheresis-and-emerging-therapies
#3
Anja Vogt
A high level of lipoprotein(a) (Lp(a)) is recognized as an independent and additional cardiovascular risk factor contributing to the risk of early onset and progressive course of cardiovascular disease (CVD). All lipid lowering medications in use mainly lower low density lipoprotein-cholesterol (LDL-c) with no or limited effect on levels of Lp(a). Niacin, the only component lowering Lp(a), is firstly often poorly tolerated and secondly not available anymore in many countries. A level of <50 mg/dl was recommended recently as the cut off level for clinical use and decision making...
February 9, 2017: Clinical Research in Cardiology Supplements
https://www.readbyqxmd.com/read/28174025/effects-of-liposome-based-local-suppression-of-nerve-growth-factor-in-the-bladder-on-autonomic-dysreflexia-during-urinary-bladder-distention-in-rats-with-spinal-cord-injury
#4
Katsumi Kadekawa, Tsuyoshi Yoshizawa, Naoki Wada, Takahiro Shimizu, Tsuyoshi Majima, Pradeep Tyagi, William C de Groat, Kimio Sugaya, Naoki Yoshimura
PURPOSE: To examine (1) whether spinal cord injury (SCI) time-dependently increases the severity of autonomic dysreflexia (AD) and expression levels of bladder nerve growth factor (NGF) protein, and (2) whether local suppression of NGF in the bladder improves SCI-induced AD in rats. MATERIALS AND METHODS: SCI was produced by the transection of the T2/3 spinal cord in female Sprague-Dawley rats. At 4 or 8weeks after SCI, differences in the mean arterial blood pressure (ΔMAP) and heart rate (ΔMHR) during graded increases in intravesical pressure to 20, 40 and 60cm H2O from those before bladder distention and NGF protein levels in the bladder wall were evaluated in spinal intact and SCI rats under urethane anesthesia...
February 4, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28148841/platelet-localized-fxi-promotes-a-vascular-coagulation-inflammatory-circuit-in-arterial-hypertension
#5
Sabine Kossmann, Jeremy Lagrange, Sven Jäckel, Kerstin Jurk, Moritz Ehlken, Tanja Schönfelder, Yvonne Weihert, Maike Knorr, Moritz Brandt, Ning Xia, Huige Li, Andreas Daiber, Matthias Oelze, Christoph Reinhardt, Karl Lackner, Andras Gruber, Brett Monia, Susanne H Karbach, Ulrich Walter, Zaverio M Ruggeri, Thomas Renné, Wolfram Ruf, Thomas Münzel, Philip Wenzel
Multicellular interactions of platelets, leukocytes, and the blood vessel wall support coagulation and precipitate arterial and venous thrombosis. High levels of angiotensin II cause arterial hypertension by a complex vascular inflammatory pathway that requires leukocyte recruitment and reactive oxygen species production and is followed by vascular dysfunction. We delineate a previously undescribed, proinflammatory coagulation-vascular circuit that is a major regulator of vascular tone, blood pressure, and endothelial function...
February 1, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28128058/apolipoprotein-a-antisense-oligonucleotides-a-new-treatment-option-for-lowering-elevated-lipoprotein-a
#6
Julia Schreml, Ioanna Gouni-Berthold
BACKGROUND: Lipoprotein(a) [Lp(a)] is a particle similar to LDL that contains an additional protein called apolipoprotein(a) [apo(a)]. Recent epidemiologic and Mendelian randomization studies have provided evidence that Lp(a) may be causally related to the pathogenesis of atherosclerosis and cardiovascular disease (CVD). While the risk association between Lp(a) concentrations and CVD is weak it seems to be continuous in shape and without an obvious threshold for Lp(a) levels. METHODS: Circulating concentrations of Lp(a) are genetically determined and desirable levels are &amp;amp;amp;amp;amp;amp;lt; 50 mg/dl...
January 25, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28078998/lipoprotein-a-management-pharmacological-and-apheretic-treatment
#7
Ruth Hanssen, Ioanna Gouni-Berthold
Lipoprotein (a) [Lp(a)] is an low-density lipoprotein (LDL)-like particle with an additional apolipoprotein, apolipoprotein (a), [apo(a)] attached to apolipoprotein B. Recent epidemiologic and Mendelian randomization studies have provided evidence that Lp(a) is causally related to the pathogenesis of atherosclerosis and cardiovascular disease (CVD). The risk association between Lp(a) concentrations and CVD is still controversial but seems to be continuous and without an obvious threshold Lp(a) level. Circulating concentrations of Lp(a) are genetically determined; desirable levels are amplt; 50 mg/dl...
12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28059953/lipoprotein-a-new-insights-from-modern-genomics
#8
Mehdi Afshar, George Thanassoulis
PURPOSE OF REVIEW: Lipoprotein(a) [Lp(a)] is the strongest independent genetic risk factor for both myocardial infarction and aortic stenosis. It has also been associated with other forms of atherosclerotic cardiovascular disease (CVD) including ischemic stroke. Its levels are genetically determined and remain fairly stable throughout life. Elevated Lp(a), above 50 mg/dl, affects one in five individuals worldwide. RECENT FINDINGS: Herein, we review the recent epidemiologic and genetic evidence supporting the causal role of Lp(a) in CVD, highlight recommendations made by European and Canadian guidelines regarding Lp(a) and summarize the rapidly evolving field of Lp(a)-lowering therapies including antisense therapies and Proprotein Convertase Subtilisin/Kexin Type 9 inhibitors...
January 5, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/27884961/therapeutic-silencing-of-fat-specific-protein-27-improves-glycemic-control-in-mouse-models-of-obesity-and-insulin-resistance
#9
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...
January 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/27797643/modern-management-of-familial-hypercholesterolemia
#10
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
#11
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
#12
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
#13
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
#14
REVIEW
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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