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Cardiovascular genomic

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https://www.readbyqxmd.com/read/28645930/genomic-and-non-genomic-effects-of-androgens-in-the-cardiovascular-system-clinical-implications
#1
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
#2
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
#3
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
#4
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
https://www.readbyqxmd.com/read/28633205/advancing-the-science-of-myocardial-recovery-with-mechanical-circulatory-support-a-working-group-of-the-national-heart-lung-and-blood-institute
#5
EDITORIAL
Stavros G Drakos, Francis D Pagani, Martha S Lundberg, Timothy J 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, and Blood Institute (NHLBI) convened a Working Group of experts from June 2 to 3, 2016, in Bethesda, Maryland, to develop NHLBI recommendations aimed at advancing the science of cardiac recovery in the setting of mechanical circulatory support (MCS). MCS devices effectively reduce volume and pressure overload that drives the cycle of progressive myocardial dysfunction, thereby triggering structural and functional reverse remodeling...
July 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28629892/engineered-myocardium-model-to-study-the-roles-of-hif-1%C3%AE-and-hif1a-as1-in-paracrine-only-signaling-under-pathological-level-oxidative-stress
#6
Aylin Acun, Pinar Zorlutuna
Studying heart tissue is critical for understanding and developing treatments for cardiovascular diseases. In this work, we fabricated precisely controlled and biomimetic engineered model tissues to study how cell-cell and cell-matrix interactions influence myocardial cell survival upon exposure to pathological level oxidative stress. Specifically, the interactions of endothelial cells (ECs) and cardiomyocytes (CMs), and the role of hypoxia inducible factor-1α (HIF-1α), with its novel alternative regulator, HIF-1α antisense RNA1 (HIF1A-AS1), in these interactions were investigated...
June 16, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28628359/the-genetic-basis-for-sex-differences-in-obesity-and-lipid-metabolism
#7
Jenny C Link, Karen Reue
Men and women exhibit significant differences in obesity, cardiovascular disease, and diabetes. To provide better diagnosis and treatment for both sexes, it is important to identify factors that underlie the observed sex differences. Traditionally, sex differences have been attributed to the differential effects of male and female gonadal secretions (commonly referred to as sex hormones), which substantially influence many aspects of metabolism and related diseases. Less appreciated as a contributor to sex differences are the fundamental genetic differences between males and females, which are ultimately determined by the presence of an XX or XY sex chromosome complement...
June 19, 2017: Annual Review of Nutrition
https://www.readbyqxmd.com/read/28623250/adamts-7-is-associated-with-a-high-risk-plaque-phenotype-in-human-atherosclerosis
#8
Eva Bengtsson, Karin Hultman, Pontus Dunér, Giuseppe Asciutto, Peter Almgren, Marju Orho-Melander, Olle Melander, Jan Nilsson, Anna Hultgårdh-Nilsson, Isabel Gonçalves
Several large-scale genome-wide association studies have identified single-nucleotide polymorphisms in the genomic region of A Disintegrin And Metalloproteinase with ThromboSpondin type 1 repeats (ADAMTS)-7 and associations to coronary artery disease. Experimental studies have provided evidence for a functional role of ADAMTS-7 in both injury-induced vascular neointima formation and development of atherosclerotic lesions. However, whether ADAMTS-7 is associated with a specific plaque phenotype in humans has not been investigated...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28623160/basic-concepts-in-molecular-biology-related-to-genetics-and-epigenetics
#9
Dolores Corella, Jose M Ordovas
The observation that "one size does not fit all" for the prevention and treatment of cardiovascular disease, among other diseases, has driven the concept of precision medicine. The goal of precision medicine is to provide the best-targeted interventions tailored to an individual's genome. The human genome is composed of billions of sequence arrangements containing a code that controls how genes are expressed. This code depends on other nonstatic regulators that surround the DNA and constitute the epigenome...
June 13, 2017: Revista Española de Cardiología
https://www.readbyqxmd.com/read/28620183/de-novo-assembly-and-annotation-of-the-zhe-maidong-ophiopogon-japonicus-l-f-ker-gawl-transcriptome-in-different-growth-stages
#10
Huijun Liu, Ying Wang, Tingzhang Wang, Xuhui Ying, Rongrong Wu, Huan Chen
Zhe-Maidong (Ophiopogon japonicus (L.f.) Ker-Gawl) is a traditional medicinal herb in the family Liliaceae that has significant pharmacological effects on immunity and cardiovascular disease. In this study, three different growth stages of Zhe-Maidong were investigated using RNA-seq, and a total of 16.4 Gb of raw data was obtained. After filtering and assembling, 96,738 unigenes with an average length of 605.3 bp were ultimately generated. A total of 77,300 unigenes were annotated using information from five databases, including the NT, NR, SwissProt, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28620071/multiancestry-study-of-gene-lifestyle-interactions-for-cardiovascular-traits-in-610-475-individuals-from-124-cohorts-design-and-rationale
#11
D C Rao, Yun J Sung, Thomas W Winkler, Karen Schwander, Ingrid Borecki, L Adrienne Cupples, W James Gauderman, Kenneth Rice, Patricia B Munroe, Bruce M Psaty
BACKGROUND: Several consortia have pursued genome-wide association studies for identifying novel genetic loci for blood pressure, lipids, hypertension, etc. They demonstrated the power of collaborative research through meta-analysis of study-specific results. METHODS AND RESULTS: The Gene-Lifestyle Interactions Working Group was formed to facilitate the first large, concerted, multiancestry study to systematically evaluate gene-lifestyle interactions. In stage 1, genome-wide interaction analysis is performed in 53 cohorts with a total of 149 684 individuals from multiple ancestries...
June 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28619369/mechanisms-of-atherosclerosis-and-cardiovascular-disease-in-antiphospholipid-syndrome-and-systemic-lupus-erythematosus-new-therapeutic-approaches
#12
REVIEW
Chary Lopez-Pedrera, M Ángeles Aguirre-Zamorano, Carlos Pérez-Sánchez
Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are 2 highly related autoimmune-rheumatic diseases associated with an increased risk of developing cardiovascular (CV) diseases. Despite the great progresses made in understanding the pathological mechanisms leading to CV diseases in those pathologies, there is still the unmet need to improve long term prognosis. CV diseases in SLE and APS is thought to happen as the result of a complex interaction between traditional CV risk factors, immune deregulation and disease activity, including the synergic effect of cytokines, chemokines, adipokines, proteases, autoantibodies, adhesion receptors, oxidative stress and a plethora of intracellular signalling molecules...
June 12, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/28615213/experimental-and-human-evidence-for-lipocalin-2-neutrophil-gelatinase-associated-lipocalin-ngal-in-the-development-of-cardiac-hypertrophy-and-heart-failure
#13
Francine Z Marques, Priscilla R Prestes, Sean G Byars, Scott C Ritchie, Peter Würtz, Sheila K Patel, Scott A Booth, Indrajeetsinh Rana, Yosuke Minoda, Stuart P Berzins, Claire L Curl, James R Bell, Bryan Wai, Piyush M Srivastava, Antti J Kangas, Pasi Soininen, Saku Ruohonen, Mika Kähönen, Terho Lehtimäki, Emma Raitoharju, Aki Havulinna, Markus Perola, Olli Raitakari, Veikko Salomaa, Mika Ala-Korpela, Johannes Kettunen, Maree McGlynn, Jason Kelly, Mary E Wlodek, Paul A Lewandowski, Lea M Delbridge, Louise M Burrell, Michael Inouye, Stephen B Harrap, Fadi J Charchar
BACKGROUND: Cardiac hypertrophy increases the risk of developing heart failure and cardiovascular death. The neutrophil inflammatory protein, lipocalin-2 (LCN2/NGAL), is elevated in certain forms of cardiac hypertrophy and acute heart failure. However, a specific role for LCN2 in predisposition and etiology of hypertrophy and the relevant genetic determinants are unclear. Here, we defined the role of LCN2 in concentric cardiac hypertrophy in terms of pathophysiology, inflammatory expression networks, and genomic determinants...
June 14, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28614576/the-hope-and-hype-of-crispr-cas9-genome-editing-a-review
#14
Kiran Musunuru
Importance: Clustered regularly interspaced short palindromic repeats (CRISPR) CRISPR-associated protein 9 (CRISPR-Cas9) has garnered a great degree of attention since its first reported uses in mammalian cells in early 2013 due to its perceived impact with respect to potential research applications and, especially, therapeutic applications. Observations: CRISPR-Cas9 is being widely used in the laboratory and has greatly improved the ability to generate genetically modified animal models of human diseases...
June 14, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28609607/blood-pathway-analyses-reveal-differences-between-prediabetic-subjects-with-or-without-dyslipidaemia-the-cardiovascular-risk-in-young-finns-study
#15
Jaakko Laaksonen, Tuukka Taipale, Ilkka Seppälä, Emma Raitoharju, Nina Mononen, Leo-Pekka Lyytikäinen, Melanie Waldenberger, Thomas Illig, Nina Hutri-Kähönen, Tapani Rönnemaa, Markus Juonala, Jorma Viikari, Mika Kähönen, Olli Raitakari, Terho Lehtimäki
BACKGROUND: Prediabetes (PR) often occurs together with dyslipidaemia (D), which is paradoxically treated with statins predisposing to type 2 diabetes mellitus. We examined peripheral blood pathway profiles in prediabetic subjects with (PRD ) and without dyslipidaemia (PR0 ) and compared these to non-prediabetic controls (C) without dyslipidaemia (C0 ). METHODS: The participants were from the Cardiovascular Risk in Young Finns Study, including 1,240 subjects aged 34-49 years...
June 13, 2017: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/28606381/which-origin-for-polycystic-ovaries-syndrome-genetic-environmental-or-both
#16
Patrick Fenichel, Charlotte Rougier, Sylvie Hieronimus, Nicolas Chevalier
Polycystic ovaries syndrome (PCOS), the most common female endocrine disorder, affects 7-10% of women of childbearing age. It includes ovarian hyperandrogenism, impaired follicular maturation, anovulation and subfertility. Insulin resistance, although present in most cases, is not necessary for diagnosis. It increases hyperandrogenism and long-term metabolic, cardiovascular and oncological risks. The origin of hyperandrogenism and hyperinsulinemia has a genetic component, as demonstrated by familial aggregation studies and recent identification of associated genomic variants, conferring a particular susceptibility to the syndrome...
June 9, 2017: Annales D'endocrinologie
https://www.readbyqxmd.com/read/28603781/genome-wide-association-studies-candidate-gene-to-dual-modifier-of-nonalcoholic-steatohepatitis-and-atherosclerosis
#17
Clint L Miller, Nicholas J Leeper
Non-alcoholic steatohepatitis (NASH) is a common disease involving chronic accumulation of fat and inflammation in the liver, often leading to advanced fibrosis, cirrhosis and cancer. It is known that NASH shares many features with atherosclerosis, however, there are still no effective therapeutics. In a recent study published in Nature, investigators demonstrate that mice lacking a high-density lipoprotein (HDL)-associated gene were surprisingly protected from both steatohepatitis and atherosclerosis through the stabilization of the liver X receptor (LXR)...
December 2016: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28592606/high-dietary-phosphorus-density-is-a-risk-factor-for-incident-chronic-kidney-disease-development-in-diabetic-subjects-a-community-based-prospective-cohort-study
#18
Chang-Yun Yoon, Jung Tak Park, Jong Hyun Jhee, Juhwan Noh, Youn Kyung Kee, Changhwan Seo, Misol Lee, Min-Uk Cha, Hyoungnae Kim, Seohyun Park, Hae-Ryong Yun, Su-Young Jung, Seung Hyeok Han, Tae-Hyun Yoo, Shin-Wook Kang
Background: High serum phosphorus concentrations are associated with an increased risk of cardiovascular disease and progression of chronic kidney disease (CKD). However, the relation between dietary phosphorus intake and CKD development has not been well evaluated.Objective: In this study, we investigated the impact of dietary phosphorus density on the development of incident CKD in a cohort of subjects with normal renal function.Design: Data were retrieved from the Korean Genome and Epidemiology Study, a prospective community-based cohort study...
June 7, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28589536/distinguishing-pathogenic-mutations-from-background-genetic-noise-in-cardiology-the-use-of-large-genome-databases-for-genetic-interpretation
#19
REVIEW
Jonas Ghouse, Morten W Skov, Robert S Bigseth, Gustav Ahlberg, Jørgen K Kanters, Morten S Olesen
Advances in clinical genetic testing has led to increased insight into the human genome, including how challenging it is to interpret rare genetic variation. In some cases, the ability to detect genetic mutations exceeds the ability to understand their clinical impact, limiting the advantage of these technologies. Obstacles in genomic medicine are many and include: understanding the level of certainty/uncertainty behind pathogenicity determination, the numerous different variant interpretation-guidelines used by clinical laboratories, delivering the certain or uncertain result to the patient, helping patients evaluate medical decisions in light of uncertainty regarding the consequence of the findings...
June 6, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28588742/folate-deficiency-as-predisposing-factor-for-childhood-leukaemia-a-review-of-the-literature
#20
REVIEW
Catia Daniela Cantarella, Denise Ragusa, Marco Giammanco, Sabrina Tosi
BACKGROUND: Folic acid and its derivates, known as folates, are chemoprotective micronutrients of great interest because of their essential role in the maintenance of health and genomic integrity. The supplementation of folic acid during pregnancy has long been known to reduce the risk of neural tube defects (NTDs) in the foetus. Folate metabolism can be altered by many factors, including adequate intake through diet. Folate deficiency can compromise the synthesis, repair and methylation of DNA, with deleterious consequences on genomic stability and gene expression...
2017: Genes & Nutrition
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