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Cardiovascular genomic

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https://www.readbyqxmd.com/read/28442232/a-genetic-risk-score-predicts-cardiovascular-events-in-patients-with-stable-coronary-artery-disease
#1
Morten Krogh Christiansen, Mette Nyegaard, Sanne Bøjet Larsen, Erik Lerkevang Grove, Morten Würtz, Søs Neergaard-Petersen, Anne-Mette Hvas, Henrik Kjærulf Jensen, Steen Dalby Kristensen
BACKGROUND: Genetic risk scores (GRSs) may predict cardiovascular risk in community-based populations. However, studies investigating the association with recurrent cardiovascular events in patients with established coronary artery disease (CAD) are conflicting. METHODS: We genotyped 879 patients with high-risk stable CAD and created a GRS based on 45 single nucleotide polymorphisms previously reported to be associated with CAD in genome-wide association studies...
April 19, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28441463/rapidsnps-a-new-computational-pipeline-for-rapidly-identifying-key-genetic-variants-reveals-previously-unidentified-snps-that-are-significantly-associated-with-individual-platelet-responses
#2
Bajuna Rashid Salehe, Chris Ian Jones, Giuseppe Di Fatta, Liam James McGuffin
Advances in omics technologies have led to the discovery of genetic markers, or single nucleotide polymorphisms (SNPs), that are associated with particular diseases or complex traits. Although there have been significant improvements in the approaches used to analyse associations of SNPs with disease, further optimised and rapid techniques are needed to keep up with the rate of SNP discovery, which has exacerbated the 'missing heritability' problem. Here, we have devised a novel, integrated, heuristic-based, hybrid analytical computational pipeline, for rapidly detecting novel or key genetic variants that are associated with diseases or complex traits...
2017: PloS One
https://www.readbyqxmd.com/read/28439531/genome-and-cd4-t-cell-methylome-wide-association-study-of-circulating-trimethylamine-n-oxide-in-the-genetics-of-lipid-lowering-drugs-and-diet-network-goldn
#3
Stella Aslibekyan, Marguerite R Irvin, Bertha A Hidalgo, Rodney T Perry, Elias J Jeyarajah, Erwin Garcia, Irina Shalaurova, Paul N Hopkins, Michael A Province, Hemant K Tiwari, Jose M Ordovas, Devin M Absher, Donna K Arnett
BACKGROUND: Trimethylamine-N-oxide (TMAO), an atherogenic metabolite species, has emerged as a possible new risk factor for cardiovascular disease. Animal studies have shown that circulating TMAO levels are regulated by genetic and environmental factors. However, large-scale human studies have failed to replicate the observed genetic associations, and epigenetic factors such as DNA methylation have never been examined in relation to TMAO levels. METHODS AND RESULTS: We used data from the family-based Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) to investigate the heritable determinants of plasma TMAO in humans...
June 2017: Journal of Nutrition & Intermediary Metabolism
https://www.readbyqxmd.com/read/28438806/emerging-affinity-based-proteomic-technologies-for-large-scale-plasma-profiling-in-cardiovascular-disease
#4
REVIEW
J Gustav Smith, Robert E Gerszten
Plasma biomarkers that reflect molecular states of the cardiovascular system are central for clinical decision making. Routinely used plasma biomarkers include troponins, natriuretic peptides, and lipoprotein particles, yet interrogate only a modest subset of pathways relevant to cardiovascular disease. Systematic profiling of a larger portion of circulating plasma proteins (the plasma proteome) will provide opportunities for unbiased discovery of novel markers to improve diagnostic or predictive accuracy. In addition, proteomic profiling may inform pathophysiological understanding and point to novel therapeutic targets...
April 25, 2017: Circulation
https://www.readbyqxmd.com/read/28437675/whole-blood-sequencing-reveals-circulating-microrna-associations-with-high-risk-traits-in-non-st-segment-elevation-acute-coronary-syndrome
#5
Alice Wang, Lydia Coulter Kwee, Elizabeth Grass, Megan L Neely, Simon G Gregory, Keith A A Fox, Paul W Armstrong, Harvey D White, E Magnus Ohman, Matthew T Roe, Svati H Shah, Mark Y Chan
BACKGROUND AND AIMS: Although circulating microRNA (miRNAs) have emerged as biomarkers predicting mortality in acute coronary syndrome (ACS), more data are needed to understand these mechanisms. Mapping miRNAs to high-risk traits may identify miRNAs involved in pathways conferring risk for poor outcome in ACS. We aim to investigate the relationship between circulating miRNAs and high-risk traits in non-ST-segment elevation acute coronary syndrome (NSTE-ACS). METHODS: Whole-genome miRNA sequencing was performed on RNA extracted from whole blood of 199 patients with NSTE-ACS...
March 30, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28435278/genetic-factors-in-pathogenesis-of-diabetes-mellitus-after-kidney-transplantation
#6
REVIEW
Maciej Tarnowski, Sylwia Słuczanowska-Głabowska, Andrzej Pawlik, Małgorzata Mazurek-Mochol, Elżbieta Dembowska
Posttransplant diabetes mellitus (PTDM) is one of the major metabolic complications after transplantation of solid organs including the kidney. This type of diabetes mellitus affects allograft survival, cardiovascular complications and overall patient survival. The modifiable risk factors that contribute to PTDM include obesity, some viral infections (eg, hepatitis C virus, cytomegalovirus) and especially immunosuppressive drugs including corticosteroids, tacrolimus, cyclosporine and sirolimus. Currently, predisposing genetic factors have been considered important in PTDM development...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28433665/advancing-the-science-of-myocardial-recovery-with-mechanical-circulatory-support-a-working-group-of-the-national-heart-lung-and-blood-institute
#7
Stavros G Drakos, Francis D Pagani, Martha S Lundberg, J Timothy Baldwin
The medical burden of heart failure (HF) has spurred interest in clinicians and scientists to develop therapies to restore the function of a failing heart. To advance this agenda, the National Heart Lung Blood Institute (NHLBI) convened a Working Group of experts on June 2-3, 2016 in Bethesda Maryland to develop recommendations for the NHLBI aimed at advancing the science of cardiac recovery in the setting of mechanical circulatory support (MCS). MSC devices effectively reduce volume and pressure overload that drives the cycle of progressive myocardial dysfunction, thereby triggering structural and functional reverse remodeling...
April 19, 2017: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/28430919/non-coding-rnas-in-cardiovascular-diseases-diagnostic-and-therapeutic-perspectives
#8
Wolfgang Poller, Stefanie Dimmeler, Stephane Heymans, Tanja Zeller, Jan Haas, Mahir Karakas, David-Manuel Leistner, Philipp Jakob, Shinichi Nakagawa, Stefan Blankenberg, Stefan Engelhardt, Thomas Thum, Christian Weber, Benjamin Meder, Roger Hajjar, Ulf Landmesser
Recent research has demonstrated that the non-coding genome plays a key role in genetic programming and gene regulation during development as well as in health and cardiovascular disease. About 99% of the human genome do not encode proteins, but are transcriptionally active representing a broad spectrum of non-coding RNAs (ncRNAs) with important regulatory and structural functions. Non-coding RNAs have been identified as critical novel regulators of cardiovascular risk factors and cell functions and are thus important candidates to improve diagnostics and prognosis assessment...
April 18, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28430547/enhancing-insights-into-pulmonary-vascular-disease-pvd-through-a-precision-medicine-approach-a-joint-nhlbi-cmref-workshop-report
#9
John H Newman, Stuart Rich, Steven H Abman, John H Alexander, John Barnard, Gerald J Beck, Raymond L Benza, Todd M Bull, Stephen Y Chan, Hyung J Chun, Declan Doogan, Jocelyn Dupuis, Serpil C Erzurum, Robert P Frantz, Mark Geraci, Hunter Gillies, Mark Gladwin, Michael P Gray, Anna R Hemnes, Roy S Herbst, Adrian F Hernandez, Nicholas S Hill, Evelyn M Horn, Kendall Hunter, Zhi-Cheng Jing, Roger Johns, Sanjay Kaul, Steven M Kawut, Tim Lahm, Jane A Leopold, Greg D Lewis, Stephen C Mathai, Vallerie V McLaughlin, Evangelos D Michelakis, Steven D Nathan, William Nichols, Grier Page, Marlene Rabinovitch, Jonathan Rich, Franz Rischard, Sharon Rounds, Sanjiv J Shah, Victor F Tapson, Naomi Lowy, Norman Stockbridge, Gail Weinmann, Lei Xiao
The Division of Lung Diseases of the National Heart, Lung and Blood Institute, (NHLBI) and the Cardiovascular Medical Education and Research Fund (CMREF), held a workshop to discuss to leverage of the anticipated scientific output from the recently launched "Redefining Pulmonary Hypertension (PH) through Pulmonary Vascular Disease Phenomics" (PVDOMICS) program. PVDOMICS is a protocol driven network to analyze PH patient populations to define novel pulmonary vascular disease (PVD) phenotypes. Basic, translational and clinical investigators, patient advocacy organizations, regulatory agencies, and pharmaceutical industry experts discussed the application of precision medicine to PVD clinical trials...
April 21, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28429242/genetics-of-dyslipidemia-and-ischemic-heart-disease
#10
REVIEW
Kavita Sharma, Ragavendra R Baliga
PURPOSE OF REVIEW: Genetic dyslipidemias contribute to the prevalence of ischemic heart disease. The field of genetic dyslipidemias and their influence on atherosclerotic heart disease is rapidly developing and accumulating increasing evidence. The purpose of this review is to describe the current state of knowledge in regard to inherited atherogenic dyslipidemias. The disorders of familial hypercholesterolemia (FH) and elevated lipoprotein(a) will be detailed. Genetic technology has made rapid advancements, leading to new discoveries in inherited atherogenic dyslipidemias, which will be explored in this review, as well as a description of possible future developments...
May 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28425521/chemical-genomic-analysis-of-gpr35-signaling
#11
Heidi Haibei Hu, Huayun Deng, Shizhang Ling, Haiyan Sun, Terry Kenakin, Xinmiao Liang, Ye Fang
GPR35, a family A orphan G protein-coupled receptor, has been implicated in inflammatory, neurological, and cardiovascular diseases. However, not much is known about the signaling and functions of GPR35. We performed a label-free kinome short hairpin RNA screen and identified a putative signaling network of GPR35 in HT-29 cells, some of which was validated using gene expression, biochemical and cellular assays. The results showed that GPR35 induced hypoxia-inducible factor 1α, and was involved in synaptic transmission, sensory perception, the immune system, and morphogenetic processes...
April 20, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28412860/modeling-vascular-inflammation-and-atherogenicity-after-inhalation-of-ambient-levels-of-ozone-exploratory-lessons-from-transcriptomics
#12
Andrea Tham, Dominic Lullo, Sarah Dalton, Siyang Zeng, Ian van Koeverden, Mehrdad Arjomandi
BACKGROUND: Epidemiologic studies have linked inhalation of air pollutants such as ozone to cardiovascular mortality. Human exposure studies have shown that inhalation of ambient levels of ozone causes airway and systemic inflammation and an imbalance in sympathetic/parasympathetic tone. METHODS: To explore molecular mechanisms through which ozone inhalation contributes to cardiovascular mortality, we compared transcriptomics data previously obtained from bronchoalveolar lavage (BAL) cells obtained from healthy subjects after inhalational exposure to ozone (200 ppb for 4 h) to those of various cell samples from 11 published studies of patients with atherosclerotic disease using the Nextbio genomic data platform...
April 16, 2017: Inhalation Toxicology
https://www.readbyqxmd.com/read/28412522/small-non-coding-rnas-in-adipocyte-biology-and-obesity
#13
REVIEW
Ez-Zoubir Amri, Marcel Scheideler
Obesity has reached epidemic proportions world-wide and constitutes a substantial risk factor for hypertension, type 2 diabetes, cardiovascular diseases and certain cancers. So far, regulation of energy intake by dietary and pharmacological treatments has met limited success. The main interest of current research is focused on understanding the role of different pathways involved in adipose tissue function and modulation of its mass. Whole-genome sequencing studies revealed that the majority of the human genome is transcribed, with thousands of non-protein-coding RNAs (ncRNA), which comprise small and long ncRNAs...
April 12, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28411266/genetic-variation-at-the-sulfonylurea-receptor-type-2-diabetes-and-coronary-heart-disease
#14
Connor A Emdin, Derek Klarin, Pradeep Natarajan, Jose C Florez, Sekar Kathiresan, Amit V Khera
Despite widespread clinical use in the treatment of type 2 diabetes, the impact of sulfonylurea therapy on cardiovascular outcomes remains uncertain. Studies of naturally occurring genetic variation can be used to anticipate the expected clinical consequences of a pharmacologic therapy. A common missense variant in the gene encoding a component of the sulfonylurea receptor (ABCC8 p.A1369S) promotes closure of the target channel of sulfonylurea therapy and is associated with increased insulin secretion, thus mimicking the effects of sulfonylurea therapy...
April 14, 2017: Diabetes
https://www.readbyqxmd.com/read/28408707/admixture-mapping-of-subclinical-atherosclerosis-and-subsequent-clinical-events-among-african-americans-in-2-large-cohort-studies
#15
Aditi Shendre, Howard Wiener, Marguerite R Irvin, Degui Zhi, Nita A Limdi, Edgar T Overton, Christina L Wassel, Jasmin Divers, Jerome I Rotter, Wendy S Post, Sadeep Shrestha
BACKGROUND: Local ancestry may contribute to the disproportionate burden of subclinical and clinical cardiovascular disease among admixed African Americans compared with other populations, suggesting a rationale for admixture mapping. METHODS AND RESULTS: We estimated local European ancestry (LEA) using Local Ancestry inference in adMixed Populations using Linkage Disequilibrium method (LAMP-LD) and evaluated the association with common carotid artery intima-media thickness (cCIMT) using multivariable linear regression analysis among 1554 African Americans from MESA (Multi-Ethnic Study of Atherosclerosis)...
April 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28408026/the-aging-cardiovascular-system-understanding-it-at-the-cellular-and-clinical-levels
#16
REVIEW
Francesco Paneni, Candela Diaz Cañestro, Peter Libby, Thomas F Lüscher, Giovanni G Camici
Cardiovascular disease (CVD) presents a great burden for elderly patients, their caregivers, and health systems. Structural and functional alterations of vessels accumulate throughout life, culminating in increased risk of developing CVD. The growing elderly population worldwide highlights the need to understand how aging promotes CVD in order to develop new strategies to confront this challenge. This review provides examples of some major unresolved clinical problems encountered in daily cardiovascular practice as we care for elderly patients...
April 18, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28401726/the-genomic-potential-of-the-aspirin-in-reducing-events-in-the-elderly-and-statins-in-reducing-events-in-the-elderly-studies
#17
Paul Lacaze, Robyn Woods, Sophia Zoungas, John McNeil
Human genetic studies are continuing to increase in size and scale, but the availability of well-phenotyped longitudinal cohorts remains rare. Significant infrastructure, investment and effort are required to establish and maintain high-quality cohorts with biobanking, genetic consent and repeated clinical data measurements. Australia currently has two such cohorts established by Monash University as part of community-based clinical trials in the elderly. Both studies involve capture of demographic, mood, cognitive performance, physical function, neuroimaging, audiometry and various clinical data types over an average of 5 years...
April 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28400104/the-state-of-cardiovascular-genomics-abundant-data-limited-information
#18
Stella Aslibekyan, Edward A Ruiz-Narváez
No abstract text is available yet for this article.
April 8, 2017: Revista Española de Cardiología
https://www.readbyqxmd.com/read/28399889/cardiac-pathology-in-spinal-muscular-atrophy-a-systematic-review
#19
REVIEW
C A Wijngaarde, A C Blank, M Stam, R I Wadman, L H van den Berg, W L van der Pol
BACKGROUND: Hereditary proximal spinal muscular atrophy (SMA) is a severe neuromuscular disease of childhood caused by homozygous loss of function of the survival motor neuron (SMN) 1 gene. The presence of a second, nearly identical SMN gene (SMN2) in the human genome ensures production of residual levels of the ubiquitously expressed SMN protein. Alpha-motor neurons in the ventral horns of the spinal cord are most vulnerable to reduced SMN concentrations but the development or function of other tissues may also be affected, and cardiovascular abnormalities have frequently been reported both in patients and SMA mouse models...
April 11, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28398557/the-2-oxoglutarate-dependent-dioxygenase-superfamily-participates-in-tanshinone-production-of-salvia-miltiorrhiza
#20
Zhichao Xu, Jingyuan Song
Highly oxidized tanshinones are pharmacological ingredients extracted from the medicinal model plant Salvia miltiorrhiza and are mainly used to treat cardiovascular diseases. Previous studies have confirmed that cytochrome P450 mono-oxygenases (CYP450s) have a key function in the biosynthesis of tanshinones; however, no solid evidence links oxidation to the 2-oxoglutarate-dependent dioxygenase (2OGD) superfamily. Here, we identified 132 members of the DOXB and DOXC subfamilies of 2OGD by scanning the 2OG-FeII Oxy domain using a genome-wide strategy in S...
April 8, 2017: Journal of Experimental Botany
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