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Cardiovascular genomic

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https://www.readbyqxmd.com/read/28736931/genetic-variants-in-hsd17b3-smad3-and-ipo11-impact-circulating-lipids-in-response-to-fenofibrate-in-individuals-with-type-2-diabetes
#1
Daniel M Rotroff, Sonja S Pijut, Skylar W Marvel, John R Jack, Tammy M Havener, Aurora Pujol, Agatha Schluter, Greg A Graf, Henry N Ginsberg, Hetal S Shah, He Gao, Mario-Luca Morieri, Alessandro Doria, Josyf C Mychaleckyi, Howard L McLeod, John B Buse, Michael J Wagner, Alison A Motsinger-Reif
Individuals with type 2 diabetes (T2D) and dyslipidemia are at an increased risk of cardiovascular disease. Fibrates are a class of drugs prescribed to treat dyslipidemia, but variation in response has been observed. To evaluate common and rare genetic variants that impact lipid responses to fenofibrate in statin-treated T2D patients, we examined lipid changes in response to fenofibrate therapy using genome-wide association(GWA). Associations were followed-up using gene expression studies in mice. Common variants in SMAD3 and IPO11 were marginally associated with lipid changes in black subjects(p<5x10(-6) )...
July 24, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28736756/advancing-the-science-of-myocardial-recovery-with-mechanical-circulatory-support-a-working-group-of-the-national-heart-lung-and-blood-institute
#2
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...
June 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28734077/integrative-studies-implicate-matrix-metalloproteinase-12-as-a-culprit-gene-for-large-artery-atherosclerotic-stroke
#3
Hovsep Mahdessian, Ljubica Perisic Matic, Mariette Lengquist, Karl Gertow, Bengt Sennblad, Damiano Baldassarre, Fabrizio Veglia, Steve E Humphries, Rainer Rauramaa, Ulf de Faire, Andries J Smit, Philippe Giral, Sudhir Kurl, Elmo Mannarino, Elena Tremoli, Anders Hamsten, Per Eriksson, Ulf Hedin, Anders Mälarstig
BACKGROUND: Ischemic stroke and coronary heart disease are important contributors to the global disease burden and share atherosclerosis as the main underlying cause. Recent evidence from a genome-wide association study (GWAS) suggested that single nucleotide polymorphisms (SNP) near the MMP12 gene at chromosome 11q22.3 were associated with large-vessel ischemic stroke. Here we evaluated and extended these results by examining the relationship between MMP12 and atherosclerosis in clinical and experimental studies...
July 22, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28731861/genetic-control-of-apoprotein-a-i-and-atheroprotection-some-insights-from-inbred-strains-of-mice
#4
Godfrey S Getz, Catherine A Reardon
PURPOSE OF REVIEW: Previous epidemiological studies and studies in experimental animals have provided strong evidence for the atheroprotective effect of HDL and its major apoprotein, apolipoprotein A-I (apoA-I). Identification of genetic loci associating apoA-I/HDL with cardiovascular disease is needed to establish a causal relationship. RECENT FINDINGS: Pharmacological interventions to increase apoA-I or HDL cholesterol levels in humans are not associated with reduction in atherosclerosis...
July 20, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28724413/smoking-related-general-and-cause-specific-mortality-in-estonia
#5
Gea Kõks, Krista Fischer, Sulev Kõks
BACKGROUND: Tobacco smoking is known to be the single largest cause of premature death worldwide. The aim of present study was to analyse the effect of smoking on general and cause-specific mortality in the Estonian population. METHODS: The data from 51,756 adults in the Estonian Genome Center of the University of Tartu was used. Information on dates and causes of death was retrieved from the National Causes of Death Registry. Smoking status, general survival, general mortality and cause-specific mortality were analysed using Kaplan-Meier estimator and Cox proportional hazards models...
July 19, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28708046/analysis-of-mtnr1b-gene-polymorphisms-in-relationship-with-irs2-gene-variants-epicardial-fat-thickness-glucose-homeostasis-and-cognitive-performance-in-the-elderly
#6
Gianluigi Mazzoccoli, Mariangela Pia Dagostino, Giulia Paroni, Davide Seripa, Filomena Ciccone, Filomena Addante, Giovanni Favuzzi, Elvira Grandone, Roberto Avola, Tommaso Mazza, Caterina Fusilli, Antonio Greco, Salvatore De Cosmo
ABSTARCT Genome-wide association studies pinpointed common variants in or near the MTNR1B gene encoding MT2 melatonin receptor to be strongly associated with fasting glucose levels. IRS2 gene polymorphisms impact insulin resistance and epicardial fat (EF) thickness, which in turn is correlated with visceral adiposity, cognitive ability and risk for metabolic plus cardiovascular disease. We aimed to discover the interactions between MTNR1B and IRS2 gene polymorphisms, insulin sensitivity, EF thickness and cognitive performance in the elderly...
July 14, 2017: Chronobiology International
https://www.readbyqxmd.com/read/28704931/alterations-in-circulating-amino-acid-metabolite-ratio-associated-with-arginase-activity-are-potential-indicators-of-metabolic-syndrome-the-korean-genome-and-epidemiology-study
#7
Jiyoung Moon, Oh Yoen Kim, Garam Jo, Min-Jeong Shin
Upregulated arginase activity, which competes with nitric oxide synthase (NOS), impairs nitric oxide production and has been implicated in various metabolic disorders. This study examined whether circulating amino acid metabolite ratios are associated with arginase and NOS activities and whether arginine bioavailability is associated with metabolic syndrome (MetS). Data related to arginase and NOS activities were collected from non-diabetic Koreans without cardiovascular disease (n = 1998) in the Ansan-Ansung cohorts (2005-2006)...
July 12, 2017: Nutrients
https://www.readbyqxmd.com/read/28698603/identification-of-differentially-methylated-brca1-and-crisp2-dna-regions-as-blood-surrogate-markers-for-cardiovascular-disease
#8
Geoffrey Istas, Ken Declerck, Maria Pudenz, Katarzyna Szarc Vel Szic, Veronica Lendinez-Tortajada, Montserrat Leon-Latre, Karen Heyninck, Guy Haegeman, Jose A Casasnovas, Maria Tellez-Plaza, Clarissa Gerhauser, Christian Heiss, Ana Rodriguez-Mateos, Wim Vanden Berghe
Genome-wide Illumina InfiniumMethylation 450 K DNA methylation analysis was performed on blood samples from clinical atherosclerosis patients (n = 8) and healthy donors (n = 8) in the LVAD study (NCT02174133, NCT01799005). Multiple differentially methylated regions (DMR) could be identified in atherosclerosis patients, related to epigenetic control of cell adhesion, chemotaxis, cytoskeletal reorganisations, cell proliferation, cell death, estrogen receptor pathways and phagocytic immune responses...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28694404/-the-role-of-omics-technology-in-the-pathophysiology-diagnosis-and-treatment-of-cardiovascular-diseases
#9
Ümit Yaşar Sinan, Serkan Unlu
Although evident improvement has occurred in the diagnosis and treatment of cardiovascular disease (CVD), it is still the most important cause of mortality worldwide. The majority of the CVDs are multifactorial and polygenic. Therefore, it is logical to use genomics, proteomics, lipidomics, and metabolomics together for diagnosis and effective treatment of CVD. "Genome" is the combination of the words "gene" and "chromosome," and includes all protein-coding genes and intergenic spaces (as well as intragenic regions, or introns, within genes) in an organism...
July 2017: Türk Kardiyoloji Derneği Arşivi: Türk Kardiyoloji Derneğinin Yayın Organıdır
https://www.readbyqxmd.com/read/28684612/the-effect-of-iron-status-on-risk-of-coronary-artery-disease-a-mendelian-randomization-study
#10
Dipender Gill, Fabiola Del Greco M, Ann P Walker, Surjit K S Srai, Michael A Laffan, Cosetta Minelli
OBJECTIVE: Iron status is a modifiable trait that has been implicated in cardiovascular disease. This study uses the Mendelian randomization technique to investigate whether there is any causal effect of iron status on risk of coronary artery disease (CAD). APPROACH AND RESULTS: A 2-sample Mendelian randomization approach is used to estimate the effect of iron status on CAD risk. Three loci (rs1800562 and rs1799945 in the HFE gene and rs855791 in TMPRSS6) that are each associated with serum iron, transferrin saturation, ferritin, and transferrin in a pattern suggestive of an association with systemic iron status are used as instruments...
July 6, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28684216/evaluation-of-dna-damage-in-wistar-rat-tissues-with-hyperlipidemia-induced-by-tyloxapol
#11
Joubert Aires de Sousa, Patrícia Pereira, Mariangela da Costa Allgayer, Norma Possa Marroni, Alexandre de Barros Falcão Ferraz, Jaqueline Nascimento Picada
Hyperlipidemia is characterized by high levels of plasma triglycerides and LDL-cholesterol, accompanied by reduced HDL-cholesterol levels, and is often associated with an increased risk of cardiovascular diseases. However, few studies have shown the effects of hyperlipidemia on genomic stability. The aim of this study was to evaluate DNA damage provided by tyloxapol induced hyperlipidemia. Tyloxapol, a non-ionic surfactant, which increases the activity of the enzyme HMG-CoA reductase and decreases clearance of lipoproteins, was used to induce hyperlipidemia in Wistar rats...
July 3, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28678615/the-future-of-nutrition-nutrigenomics-and-nutrigenetics-in-obesity-and-cardiovascular-diseases
#12
Alicia Cristina Peña-Romero, Diana Navas-Carrillo, Francisco Marín, Esteban Orenes-Piñero
Over time, the relationship between diet and health has aroused great interest, since nutrition can prevent and treat several diseases. It has been demonstrated that general recommendations on macronutrients and micronutrients do not affect to every individual in the same way because diet is an important environmental factor that interacts with genes. Thus, there is a growing necessity of improving a personalized nutrition to treat obesity and associated medical conditions, taking into account the interactions between diet, genes and health...
July 5, 2017: Critical Reviews in Food Science and Nutrition
https://www.readbyqxmd.com/read/28652256/fundamental-cardiovascular-research-returns-on-societal-investment-a-scientific-statement-from-the-american-heart-association
#13
REVIEW
Joseph A Hill, Reza Ardehali, Kimberli Taylor Clarke, Gregory J Del Zoppo, Lee L Eckhardt, Kathy K Griendling, Peter Libby, Dan M Roden, Hesham A Sadek, Christine E Seidman, Douglas E Vaughan
Recent decades have witnessed robust successes in conquering the acutely lethal manifestations of heart and vascular diseases. Many patients who previously would have died now survive. Lifesaving successes like these provide a tremendous and easily recognized benefit to individuals and society. Although cardiovascular mortality has declined, the devastating impact of chronic heart disease and comorbidities on quality of life and healthcare resources continues unabated. Future strides, extending those made in recent decades, will require continued research into mechanisms underlying disease prevention, pathogenesis, progression, and therapeutic intervention...
June 26, 2017: Circulation Research
https://www.readbyqxmd.com/read/28650953/de-novo-paternal-fbn1-mutation-detected-in-embryos-before-implantation
#14
Shuling Wang, Ziru Niu, Hui Wang, Minyue Ma, Wei Zhang, Shu Fang Wang, Jun Wang, Hong Yan, Yifan Liu, Na Duan, Xiandong Zhang, Yuanqing Yao
BACKGROUND Marfan syndrome (MFS) is an autosomal dominant disease caused by mutations in the Fibrillin (FBN)1 gene and characterized by disorders in the cardiovascular, skeletal, and visual systems. The diversity of mutations and phenotypic heterogeneity of MFS make prenatal molecular diagnoses difficult. In this study, we used pre-implantation genetic diagnosis (PGD) to identify the pathogenic mutation in a male patient with MFS and to determine whether his offspring would be free of the disease. MATERIAL AND METHODS The history and pedigree of the proband were analyzed...
June 26, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28648749/transcriptome-profiling-of-3d-co-cultured-cardiomyocytes-and-endothelial-cells-under-oxidative-stress-using-a-photocrosslinkable-hydrogel-system
#15
Xiaoshan Yue, Aylin Acun, Pinar Zorlutuna
Myocardial infarction (MI) is one of the most common among cardiovascular diseases. Endothelial cells (ECs) are considered to have protective effects on cardiomyocytes (CMs) under stress conditions such as MI; however, the paracrine CM-EC crosstalk and the resulting endogenous cellular responses that could contribute to this protective effect are not thoroughly investigated. Here we created biomimetic synthetic tissues containing CMs and human induced pluripotent stem cell (hiPSC)-derived ECs (iECs), which showed improved cell survival compared to single cultures under conditions mimicking the aftermath of MI, and performed high-throughput RNA-sequencing to identify target pathways that could govern CM-iEC crosstalk and the resulting improvement in cell viability...
June 23, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28648738/current-topics-in-angiotensin-ii-type-1-receptor-research-focus-on-inverse-agonism-receptor-dimerization-and-biased-agonism
#16
REVIEW
Takanobu Takezako, Hamiyet Unal, Sadashiva S Karnik, Koichi Node
Although the octapeptide hormone angiotensin II (Ang II) regulates cardiovascular and renal homeostasis through the Ang II type 1 receptor (AT1R), overstimulation of AT1R causes various human diseases, such as hypertension and cardiac hypertrophy. Therefore, AT1R blockers (ARBs) have been widely used as therapeutic drugs for these diseases. Recent basic research and clinical studies have resulted in the discovery of interesting phenomena associated with AT1R function. For example, ligand-independent activation of AT1R by mechanical stress and agonistic autoantibodies, as well as via receptor mutations, has been shown to decrease the inverse agonistic efficacy of ARBs, though the molecular mechanisms of such phenomena had remained elusive until recently...
June 23, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28645930/genomic-and-non-genomic-effects-of-androgens-in-the-cardiovascular-system-clinical-implications
#17
REVIEW
Angela K Lucas-Herald, Rheure Alves-Lopes, Augusto C Montezano, S Faisal Ahmed, Rhian M Touyz
The principle steroidal androgens are testosterone and its metabolite 5α-dihydrotestosterone (DHT), which is converted from testosterone by the enzyme 5α-reductase. Through the classic pathway with androgens crossing the plasma membrane and binding to the androgen receptor (AR) or via mechanisms independent of the ligand-dependent transactivation function of nuclear receptors, testosterone induces genomic and non-genomic effects respectively. AR is widely distributed in several tissues, including vascular endothelial and smooth muscle cells...
July 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28645652/androgen-inhibits-key-atherosclerotic-processes-by-directly-activating-adtrp-transcription
#18
Chunyan Luo, Elisabeth Pook, Bo Tang, Weiyi Zhang, Sisi Li, Kirsten Leineweber, Shing-Hu Cheung, Qiuyun Chen, Martin Bechem, Jing-Shan Hu, Volker Laux, Qing Kenneth Wang
Low androgen levels are associated with an increased risk of coronary artery disease (CAD), thrombosis and myocardial infarction (MI), suggesting that androgen has a protective role. However, little is known about the underlying molecular mechanism. Our genome-wide association study identified the ADTRP gene encoding the androgen-dependent TFPI regulating protein as a susceptibility gene for CAD and MI. The expression level of ADTRP was regulated by androgen, but the molecular mechanism is unknown. In this study, we identified the molecular mechanism by which androgen regulates ADTRP expression and tested the hypothesis that androgen plays a protective role in cardiovascular disease by activating ADTRP expression...
June 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28644415/genome-wide-association-study-of-dietary-pattern-scores
#19
Frédéric Guénard, Annie Bouchard-Mercier, Iwona Rudkowska, Simone Lemieux, Patrick Couture, Marie-Claude Vohl
Dietary patterns, representing global food supplies rather than specific nutrients or food intakes, have been associated with cardiovascular disease (CVD) incidence and mortality. The contribution of genetic factors in the determination of food intakes, preferences and dietary patterns has been previously established. The current study aimed to identify novel genetic factors associated with reported dietary pattern scores. Reported dietary patterns scores were derived from reported dietary intakes for the preceding month and were obtained through a food frequency questionnaire and genome-wide association study (GWAS) conducted in a study sample of 141 individuals...
June 23, 2017: Nutrients
https://www.readbyqxmd.com/read/28638342/warfarin-anticoagulation-therapy-in-caribbean-hispanics-of-puerto-rico-a-candidate-gene-association-study
#20
Karla Claudio-Campos, Aurora Labastida, Alga Ramos, Andrea Gaedigk, Jessicca Renta-Torres, Dariana Padilla, Giselle Rivera-Miranda, Stuart A Scott, Gualberto Ruaño, Carmen L Cadilla, Jorge Duconge-Soler
Existing algorithms account for ~50% of observed variance in warfarin dose requirements after including common polymorphisms. However, they do not perform as well in populations other than Caucasians, in part because some ethno-specific genetic variants are overlooked. The objective of the present study was to identify genetic polymorphisms that can explain variability in warfarin dose requirements among Caribbean Hispanics of Puerto Rico. Next-Generation Sequencing of candidate genes CYP2C9 and VKORC1 and genotyping by DMET® Plus Assay of cardiovascular patients were performed...
2017: Frontiers in Pharmacology
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