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https://www.readbyqxmd.com/read/29330663/human-cytomegalovirus-encoded-mir-ul112-contributes-to-hcmv-mediated-vascular-diseases-by-inducing-vascular-endothelial-cell-dysfunction
#1
Kai Shen, Liyun Xu, Dongdong Chen, Weiguo Tang, Yanyan Huang
Human cytomegalovirus (HCMV) infection has been linked to the pathogenesis of vasculopathy by inducing dysfunction of vascular cells such as endothelial cells. Hcmv-miR-UL112 is the most well-characterized HCMV-encoded microRNA occurring in the plasma of patients with cardiovascular diseases such as hypertension, while the specific underlying pathophysiological mechanisms are yet to be defined. The current study investigated the effect of hcmv-miR-UL112 on the growth and proliferation of human umbilical vascular endothelial cells (HUVECs); it might also be associated with signaling pathways...
January 12, 2018: Virus Genes
https://www.readbyqxmd.com/read/29326279/gut-microbiota-in-cardiovascular-disease-and-heart-failure
#2
REVIEW
Takeshi Kitai, W H Wilson Tang
Accumulating evidence supports a relationship between the complexity and diversity of the gut microbiota and host diseases. In addition to alterations in the gut microbial composition, the metabolic potential of gut microbiota has been identified as a contributing factor in the development of diseases. Recent technological developments of molecular and biochemical analyses enable us to detect and characterize the gut microbiota via assessment and classification of its genomes and corresponding metabolites. These advances have provided emerging data supporting the role of gut microbiota in various physiological activities including host metabolism, neurological development, energy homeostasis, and immune regulation...
January 16, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29318963/nanodiagnostics-and-nanodelivery-applications-in-genetic-alterations
#3
Maria Sofia Falzarano, Cristina Flesia, Roberta Cavalli, Caterina Guiot, Alessandra Ferlini
Background Genetic alterations cause hereditary diseases (HDs) with a wide range of incidences. Some, like cystic fibrosi, occur frequently (1/1,000 newborns), whilst others, such as Pompe disease and other metabolic disorders are very rare (1/100,000 newborns). They are well under the threshold of 1/3,000, denoted by the European Community as rare diseases (RDs). Genetic alterations are also associated with multifactorial disorders like diabetes, and underline both somatic and germline mutations in cancer...
January 10, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29316320/human-microbiota-blood-group-antigens-and-disease
#4
REVIEW
D Rose Ewald, Susan C J Sumner
Far from being just "bugs in our guts," the microbiota interacts with the body in previously unimagined ways. Research into the genome and the microbiome has revealed that the human body and the microbiota have a long-established but only recently recognized symbiotic relationship; homeostatic balance between them regulates body function. That balance is fragile, easily disturbed, and plays a fundamental role in human health-our very survival depends on the healthy functioning of these microorganisms. Increasing rates of cardiovascular, autoimmune, and inflammatory diseases, as well as epidemics in obesity and diabetes in recent decades are believed to be explained, in part, by unintended effects on the microbiota from vaccinations, poor diets, environmental chemicals, indiscriminate antibiotic use, and "germophobia...
January 9, 2018: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
https://www.readbyqxmd.com/read/29315646/microrna-21-bridging-binge-drinking-and-cardiovascular-health
#5
Yingmei Zhang, Jun Ren
Binge drinking is commonly associated with high risk of cardiovascular diseases although the underlying mechanism remains elusive. Advances in genomics and genetics have indicated a number of alcohol-responsive genes in alcohol drinking behavior and alcoholic organ injury. Recent findings revealed a dramatic rise in mircoRNA-10a (miR-10a) and miR-21 levels with binge drinking (Beech et al., 2014). Given the increased knowledge in the past decade on the role of non-coding RNAs in the regulation of cardiovascular function, the identification of novel microRNA and underlying cellular mechanisms in alcoholism and alcoholic organ complication suggests therapeutic promises for the interventions against alcoholic complications...
January 6, 2018: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29311597/putative-functional-genes-in-idiopathic-dilated-cardiomyopathy
#6
Nishanth Ulhas Nair, Avinash Das, Uri Amit, Welles Robinson, Seung Gu Park, Mahashweta Basu, Alex Lugo, Jonathan Leor, Eytan Ruppin, Sridhar Hannenhalli
Idiopathic dilated cardiomyopathy (DCM) is a complex disorder with a genetic and an environmental component involving multiple genes, many of which are yet to be discovered. We integrate genetic, epigenetic, transcriptomic, phenotypic, and evolutionary features into a method - Hridaya, to infer putative functional genes underlying DCM in a genome-wide fashion, using 213 human heart genomes and transcriptomes. Many genes identified by Hridaya are experimentally shown to cause cardiac complications. We validate the top predicted genes, via five different genome-wide analyses: First, the predicted genes are associated with cardiovascular functions...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29301854/autophagy-is-required-for-sortilin-mediated-degradation-of-apolipoprotein-b100
#7
Jaume Amengual, Liang Guo, Alanna Strong, Julio Madrigal-Matute, Haizhen Wang, Susmita Kaushik, Jeffrey L Brodsky, Daniel J Rader, Ana Maria Cuervo, Edward A Fisher
Rationale: Genome-Wide Association Studies identified single nucleotide polymorphisms (SNPs) near the SORT1 locus strongly associated with decreased plasma low-density lipoprotein cholesterol (LDL-C) levels and protection from atherosclerotic cardiovascular disease and myocardial infarction. The minor allele of the causal SORT1 SNP locus creates a putative C/EBPα binding site in the SORT1 promoter, thereby increasing sortilin expression by 12-fold in liver, which is rich in this transcription factor. Our previous studies in mice have showed reductions in plasma LDL-C and its principal protein component, apolipoprotein B (apoB) with increased SORT1 expression, and in vitro studies suggested that sortilin promoted the presecretory lysosomal degradation of apoB associated with the LDL precursor, very-low density lipoprotein (VLDL)...
January 4, 2018: Circulation Research
https://www.readbyqxmd.com/read/29300220/genomics-of-cardiovascular-measures-of-autonomic-tone
#8
Martin I Sigurdsson, Nathan H Waldron, Andrey V Bortsov, Shad B Smith, William Maixner
The autonomic nervous system exerts broad control over the involuntary functions of the human body via complex equilibrium between sympathetic and parasympathetic tone. Imbalance in this equilibrium is associated with a multitude of cardiovascular outcomes, including mortality. The cardiovascular static state of this equilibrium can be quantified via physiological parameters such as heart rate, blood pressure and by spectral analysis of heart rate variability.Here we review the current state of knowledge of the genetic background of cardiovascular measurements of autonomic tone...
January 3, 2018: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/29288185/cohort-profile-the-emory-cardiovascular-biobank-emcab
#9
Yi-An Ko, Salim Hayek, Pratik Sandesara, Ayman Samman Tahhan, Arshed Quyyumi
PURPOSE: The Emory Cardiovascular Biobank (EmCAB) is an ongoing prospective registry of patients undergoing cardiac catheterisation, which was established to identify novel factors associated with the pathobiological process and treatment of cardiovascular disease. PARTICIPANTS: Individuals aged 18 years and older undergoing cardiac catheterisation at three Emory Healthcare sites in Atlanta are asked to participate in this prospective registry. Around 95% agree to participate...
December 29, 2017: BMJ Open
https://www.readbyqxmd.com/read/29285967/the-genomic-health-of-ancient-hominins
#10
Ali J Berens, Taylor L Cooper, Joseph Lachance
The genomes of ancient humans, Neandertals, and Denisovans contain many alleles that influence disease risks. Using genotypes at 3,180 disease-associated loci, we estimated the disease burden of 147 ancient genomes. After correcting for missing data, genetic risk scores (GRS) were generated for nine disease categories and the set of all combined diseases. We used these genetic risk scores to examine the effects of different types of subsistence, geography, and sample age on the number of risk alleles in each ancient genome...
January 2017: Human Biology
https://www.readbyqxmd.com/read/29284720/overdiagnosis-across-medical-disciplines-a-scoping-review
#11
Kevin Jenniskens, Joris A H de Groot, Johannes B Reitsma, Karel G M Moons, Lotty Hooft, Christiana A Naaktgeboren
OBJECTIVE: To provide insight into how and in what clinical fields overdiagnosis is studied and give directions for further applied and methodological research. DESIGN: Scoping review. DATA SOURCES: Medline up to August 2017. STUDY SELECTION: All English studies on humans, in which overdiagnosis was discussed as a dominant theme. DATA EXTRACTION: Studies were assessed on clinical field, study aim (ie, methodological or non-methodological), article type (eg, primary study, review), the type and role of diagnostic test(s) studied and the context in which these studies discussed overdiagnosis...
December 27, 2017: BMJ Open
https://www.readbyqxmd.com/read/29279960/quantitative-trait-mapping-in-diversity-outbred-mice-identifies-two-genomic-regions-associated-with-heart-size
#12
John R Shorter, Wei Huang, Ju Youn Beak, Kunjie Hua, Daniel M Gatti, Fernando Pardo-Manuel de Villena, Daniel Pomp, Brian C Jensen
Heart size is an important factor in cardiac health and disease. In particular, increased heart weight is predictive of adverse cardiovascular outcomes in multiple large community-based studies. We use two cohorts of Diversity Outbred (DO) mice to investigate the role of genetics, sex, age, and diet on heart size. DO mice (n = 289) of both sexes from generation 10 were fed a standard chow diet, and analyzed at 12-15 weeks of age. Another cohort of female DO mice (n = 258) from generation 11 were fed either a high-fat, cholesterol-containing (HFC) diet or a low-fat, high-protein diet, and analyzed at 24-25 weeks...
December 26, 2017: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/29261184/analysis-of-publicly-available-ldlr-apob-and-pcsk9-variants-associated-with-familial-hypercholesterolemia-application-of-acmg-guidelines-and-implications-for-familial-hypercholesterolemia-diagnosis
#13
Joana Rita Chora, Ana Margarida Medeiros, Ana Catarina Alves, Mafalda Bourbon
PurposeFamilial hypercholesterolemia (FH) is an autosomal disorder of lipid metabolism presenting with increased cardiovascular risk. Although more than 1,700 variants have been associated with FH, the great majority have not been functionally proved to affect the low-density lipoprotein receptor cycle. We aimed to classify all described variants associated with FH and to establish the proportion of variants that lack evidence to support their pathogenicity.MethodsWe followed American College of Medical Genetics and Genomics (ACMG) guidelines for the classification, and collected information from a variety of databases and individual reports...
October 26, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29258991/the-genetic-architecture-of-the-cardiovascular-risk-proteome
#14
Mark D Benson, Qiong Yang, Debby Ngo, Yineng Zhu, Dongxiao Shen, Laurie A Farrell, Sumita Sinha, Michelle J Keyes, Ramachandran S Vasan, Martin G Larson, J Gustav Smith, Thomas J Wang, Robert E Gerszten
Background -We recently identified 156 proteins in human plasma that were each associated with the net Framingham Cardiovascular Disease (CVD) Risk Score (FRS) using an aptamer-based proteomic platform in Framingham Heart Study (FHS) Offspring participants. Here, we hypothesized that performing genome-wide association studies and exome array analyses on the levels of each these 156 proteins might identify genetic determinants of risk-associated circulating factors and provide insights into early cardiovascular pathophysiology...
December 19, 2017: Circulation
https://www.readbyqxmd.com/read/29248989/stratified-prevention-opportunities-and-limitations-report-on-the-1st-interdisciplinary-cardiovascular-workshop-in-augsburg
#15
Gregor Kirchhof, Josef Franz Lindner, Stephan Achenbach, Klaus Berger, Stefan Blankenberg, Heiner Fangerau, Henner Gimpel, Ulrich M Gassner, Jens Kersten, Dorothea Magnus, Herbert Rebscher, Heribert Schunkert, Stephan Rixen, Paulus Kirchhof
Sufficient exercise and sleep, a balanced diet, moderate alcohol consumption and a good approach to handle stress have been known as lifestyles that protect health and longevity since the Middle Age. This traditional prevention quintet, turned into a sextet by smoking cessation, has been the basis of the "preventive personality" that formed in the twentieth century. Recent analyses of big data sets including genomic and physiological measurements have unleashed novel opportunities to estimate individual health risks with unprecedented accuracy, allowing to target preventive interventions to persons at high risk and at the same time to spare those in whom preventive measures may not be needed or even be harmful...
December 16, 2017: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
https://www.readbyqxmd.com/read/29243114/effect-of-cytochrome-p450-2c19-polymorphism-on-adverse-cardiovascular-events-after-drug-eluting-stent-implantation-in-a-large-hakka-population-with-acute-coronary-syndrome-receiving-clopidogrel-in-southern-china
#16
Zhixiong Zhong, Jingyuan Hou, Qifeng Zhang, Bin Li, Cunren Li, Zhidong Liu, Min Yang, Wei Zhong, Xuebo He, Hesen Wu, Miaocai Zhong, Pingsen Zhao
BACKGROUND AND OBJECTIVES: The objective of this study is to evaluate the effects of cytochrome P450 2C19 (CYP2C19) polymorphism on adverse cardiovascular events (MACE) in Hakka patients with acute coronary syndrome (ACS) receiving clopidogrel who had undergone coronary drug-eluting stent placement after percutaneous coronary intervention (PCI) in southern China. METHODS: Genotyping of CYP2C19 and MACE of 934 ACS patients with PCI on clopidogrel maintenance therapy were analyzed...
December 14, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29237689/technical-advances-for-the-clinical-genomic-evaluation-of-sudden-cardiac-death-verification-of-next-generation-sequencing-panels-for-hereditary-cardiovascular-conditions-using-formalin-fixed-paraffin-embedded-tissues-and-dried-blood-spots
#17
Linnea M Baudhuin, Charles Leduc, Laura J Train, Rajeswari Avula, Michelle L Kluge, Katrina E Kotzer, Peter T Lin, Michael J Ackerman, Joseph J Maleszewski
BACKGROUND: Postmortem genetic testing for heritable cardiovascular (CV) disorders is often lacking because ideal specimens (ie, whole blood) are not retained routinely at autopsy. Formalin-fixed paraffin-embedded tissue (FFPET) is ubiquitously collected at autopsy, but DNA quality hampers its use with traditional sequencing methods. Targeted next-generation sequencing may offer the ability to circumvent such limitations, but a method has not been previously described. The primary aim of this study was to develop and evaluate the use of FFPET for heritable CV disorders via next-generation sequencing...
December 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/29237688/heritability-of-atrial-fibrillation
#18
Lu-Chen Weng, Seung Hoan Choi, Derek Klarin, J Gustav Smith, Po-Ru Loh, Mark Chaffin, Carolina Roselli, Olivia L Hulme, Kathryn L Lunetta, Josée Dupuis, Emelia J Benjamin, Christopher Newton-Cheh, Sekar Kathiresan, Patrick T Ellinor, Steven A Lubitz
BACKGROUND: Previous reports have implicated multiple genetic loci associated with AF, but the contributions of genome-wide variation to AF susceptibility have not been quantified. METHODS AND RESULTS: We assessed the contribution of genome-wide single-nucleotide polymorphism variation to AF risk (single-nucleotide polymorphism heritability, h2g ) using data from 120 286 unrelated individuals of European ancestry (2987 with AF) in the population-based UK Biobank...
December 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/29237687/metabolic-profiling-of-adiponectin-levels-in-adults-mendelian-randomization-analysis
#19
Maria Carolina Borges, Aluísio J D Barros, Diana L Santos Ferreira, Juan Pablo Casas, Bernardo Lessa Horta, Mika Kivimaki, Meena Kumari, Usha Menon, Tom R Gaunt, Yoav Ben-Shlomo, Deise F Freitas, Isabel O Oliveira, Aleksandra Gentry-Maharaj, Evangelia Fourkala, Debbie A Lawlor, Aroon D Hingorani
BACKGROUND: Adiponectin, a circulating adipocyte-derived protein, has insulin-sensitizing, anti-inflammatory, antiatherogenic, and cardiomyocyte-protective properties in animal models. However, the systemic effects of adiponectin in humans are unknown. Our aims were to define the metabolic profile associated with higher blood adiponectin concentration and investigate whether variation in adiponectin concentration affects the systemic metabolic profile. METHODS AND RESULTS: We applied multivariable regression in ≤5909 adults and Mendelian randomization (using cis-acting genetic variants in the vicinity of the adiponectin gene as instrumental variables) for analyzing the causal effect of adiponectin in the metabolic profile of ≤37 545 adults...
December 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/29237686/toward-genetics-driven-early-intervention-in-dilated-cardiomyopathy-design-and-implementation-of-the-dcm-precision-medicine-study
#20
REVIEW
Daniel D Kinnamon, Ana Morales, Deborah J Bowen, Wylie Burke, Ray E Hershberger
BACKGROUND: The cause of idiopathic dilated cardiomyopathy (DCM) is unknown by definition, but its familial subtype is considered to have a genetic component. We hypothesize that most idiopathic DCM, whether familial or nonfamilial, has a genetic basis, in which case a genetics-driven approach to identifying at-risk family members for clinical screening and early intervention could reduce morbidity and mortality. METHODS: On the basis of this hypothesis, we have launched the National Heart, Lung, and Blood Institute- and National Human Genome Research Institute-funded DCM Precision Medicine Study, which aims to enroll 1300 individuals (600 non-Hispanic African ancestry, 600 non-Hispanic European ancestry, and 100 Hispanic) who meet rigorous clinical criteria for idiopathic DCM along with 2600 of their relatives...
December 2017: Circulation. Cardiovascular Genetics
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