Read by QxMD icon Read

Antisense cardiovascular

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
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
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...
October 17, 2016: Current Opinion in Lipidology
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
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
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
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...
September 21, 2016: Lancet
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
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
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
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
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
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
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...
2016: Nature Communications
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-)
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
Philip L S M Gordts, Ryan Nock, Ni-Huiping Son, Bastian Ramms, Irene Lew, Jon C Gonzales, Bryan E Thacker, Debapriya Basu, Richard G Lee, Adam E Mullick, Mark J Graham, Ira J Goldberg, Rosanne M Crooke, Joseph L Witztum, Jeffrey D Esko
Hypertriglyceridemia is an independent risk factor for cardiovascular disease, and plasma triglycerides (TGs) correlate strongly with plasma apolipoprotein C-III (ApoC-III) levels. Antisense oligonucleotides (ASOs) for ApoC-III reduce plasma TGs in primates and mice, but the underlying mechanism of action remains controversial. We determined that a murine-specific ApoC-III-targeting ASO reduces fasting TG levels through a mechanism that is dependent on low-density lipoprotein receptors (LDLRs) and LDLR-related protein 1 (LRP1)...
August 1, 2016: Journal of Clinical Investigation
K S Wilson, C S Tucker, E A S Al-Dujaili, M C Holmes, P W F Hadoke, C J Kenyon, M A Denvir
Glucocorticoids (GCs) in utero influence embryonic development with consequent programmed effects on adult physiology and pathophysiology and altered susceptibility to cardiovascular disease. However, in viviparous species, studies of these processes are compromised by secondary maternal influences. The zebrafish, being fertilised externally, avoids this problem and has been used here to investigate the effects of transient alterations in GC activity during early development. Embryonic fish were treated either with dexamethasone (a synthetic GC), an antisense GC receptor (GR) morpholino (GR Mo), or hypoxia for the first 120h post fertilisation (hpf); responses were measured during embryonic treatment or later, post treatment, in adults...
July 2016: Journal of Endocrinology
Amir Tajbakhsh, Seyed Mahdi Hassanian, Mohammad Sadegh Khorrami, Alireza Pasdar, Ehsan Tabatabai, Seyed Mohammad Reza Parizadeh, Mostafa Fazeli, Sharareh Gholamin, Gordon A Ferns, Majid Ghayour-Mobarhan, Amir Avan
Cardiovascular disease (CVD) is the leading cause of global mortality. Although extensive efforts have been made to identify valid biomarkers for CVD risk, relatively ¬¬¬few are of proven clinical utility. It is recognized that genetic factors play a major role in determining the susceptibility to CVD. Recent genome-wide-association-studies have demonstrated common genetic variants in a region on chromosome 9p21 associated with an increased risk of CVD. Several genetic-polymorphisms have been identified in this region that are highly associated with CVD, and these are clustered around the gene loci for CDKN2B (coding for p15ink4b), CDKN2A (coding for p16ink4a and p14ARF) and the 3' end of CDKN2BAS, which has been termed antisense noncoding RNA in the INK4 locus (ANRIL)...
June 27, 2016: Current Pharmaceutical Design
Xue Liu, Ying Zhang, Weijie Du, Haihai Liang, Hua He, Lu Zhang, Zhenwei Pan, Xuelian Li, Chaoqian Xu, Yuhong Zhou, Leimin Wang, Ming Qian, Tianyi Liu, Hongli Yin, Yanjie Lu, Baofeng Yang, Hongli Shan
BACKGROUND/AIMS: Acute myocardial infarction (AMI) is a devastating cardiovascular disease with a high rate of morbidity and mortality, partly due to enhanced arrhythmogenicity. MicroRNAs (miRNAs) have been shown to participate in the regulation of cardiac ion channels and the associated arrhythmias. The purpose of this study was to test our hypothesis that miR-223-3p contributes to the electrical disorders in AMI via modulating KCND2, the gene encoding voltage-gated channel Kv4.2 that carries transient outward K+ current Ito...
2016: Cellular Physiology and Biochemistry
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"