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Hypertension targets

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https://www.readbyqxmd.com/read/28430357/reactive-oxygen-species-key-regulators-in-vascular-health-and-diseases
#1
REVIEW
Qishan Chen, Qiwen Wang, Jianhua Zhu, Qingzhong Xiao, Li Zhang
Reactive oxygen species (ROS) are a group of small reactive molecules that play critical roles in the regulation of various cell functions and biological processes. In the vascular system, physiological levels of ROS are essential for normal vascular functions including endothelial homeostasis and smooth muscle cell contraction. In contrast, uncontrolled overproduction of ROS resulted from imbalance of ROS generation and elimination, leads to the development of vascular diseases. Excessive ROS cause vascular cell damages, recruitment of inflammatory cells, lipid peroxidation, activation of metalloproteinases, and deposition of extracellular matrix, collectively leading to vascular remodeling...
April 21, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28428072/membrane-lipid-alterations-in-the-metabolic-syndrome-and-the-role-of-dietary-oils
#2
REVIEW
Javier S Perona
The metabolic syndrome is a cluster of pathological conditions, including hypertension, hyperglycemia, hypertriglyceridemia, obesity and low HDL levels that is of great concern worldwide, as individuals with metabolic syndrome have an increased risk of type-2 diabetes and cardiovascular disease. Insulin resistance, the key feature of the metabolic syndrome, might be at the same time cause and consequence of impaired lipid composition in plasma membranes of insulin-sensitive tissues like liver, muscle and adipose tissue...
April 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28427484/racial-and-ethnic-subgroup-disparities-in-hypertension-prevalence-new-york-city-health-and-nutrition-examination-survey-2013-2014
#3
Kezhen Fei, Jesica S Rodriguez-Lopez, Marcel Ramos, Nadia Islam, Chau Trinh-Shevrin, Stella S Yi, Claudia Chernov, Sharon E Perlman, Lorna E Thorpe
INTRODUCTION: Racial/ethnic minority adults have higher rates of hypertension than non-Hispanic white adults. We examined the prevalence of hypertension among Hispanic and Asian subgroups in New York City. METHODS: Data from the 2013-2014 New York City Health and Nutrition Examination Survey were used to assess hypertension prevalence among adults (aged ≥20) in New York City (n = 1,476). Hypertension was measured (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg or self-reported hypertension and use of blood pressure medication)...
April 20, 2017: Preventing Chronic Disease
https://www.readbyqxmd.com/read/28424433/-investigating-the-role-of-ceramide-metabolism-associated-cers5-lass5-gene-in-atherosclerosis-pathogenesis-in-endothelial-cells
#4
Neslihan Çoban, Filiz Güçlü Geyik, Özlem Yıldırım, Nihan Erginel Ünaltuna
OBJECTIVE: Ceramide, the backbone of sphingolipids, is the key component affecting atherosclerotic changes through its important second-messenger role. Previous studies have demonstrated protective role of AMP-activated protein kinase (AMPK) genes in regulating atherosclerosis and hypertension. Ceramide synthase 5 (LASS5 or CERS5) gene has function in de novo synthesis of ceramide, and has indirect effect on AMPK gene. Aim of the present study was to identify role of LASS5 gene in atherosclerosis...
March 2017: Türk Kardiyoloji Derneği Arşivi: Türk Kardiyoloji Derneğinin Yayın Organıdır
https://www.readbyqxmd.com/read/28422749/obesity-induced-hepatic-steatosis-is-mediated-by-endoplasmic-reticulum-stress-in-the-subfornical-organ-of-the-brain
#5
Julie A Horwath, Chansol Hurr, Scott D Butler, Mallikarjun Guruju, Martin D Cassell, Allyn L Mark, Robin L Davisson, Colin N Young
Nonalcoholic fatty liver disease (NAFLD), characterized by an excess accumulation of hepatic triglycerides, is a growing health epidemic. While ER stress in the liver has been implicated in the development of NAFLD, the role of brain ER stress - which is emerging as a key contributor to a number of chronic diseases including obesity - in NAFLD remains unclear. These studies reveal that chemical induction of ER stress in the brain caused hepatomegaly and hepatic steatosis in mice. Conversely, pharmacological reductions in brain ER stress in diet-induced obese mice rescued NAFLD independent of body weight, food intake, and adiposity...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28418458/right-ventricular-fiber-structure-as-a-compensatory-mechanism-in-experimental-pressure-overload-a-computational-study
#6
Arnold D Gomez, Huashan Zou, Megan E Bowen, Xiaoqing Liu, Edward W Hsu, Stephen H McKellar
Right ventricular failure (RVF) is a lethal condition in diverse pathologies. Pressure overload is the most common etiology of RVF, but our understanding of the tissue structure remodeling and other biomechanical factors involved in RVF is limited. Some remodeling patterns are interpreted as compensatory mechanisms including myocyte hypertrophy, extracellular fibrosis, and changes in fiber orientation. However, the specific implications of these changes, especially in relation to clinically observable measurements, are difficult to investigate experimentally...
April 17, 2017: Journal of Biomechanical Engineering
https://www.readbyqxmd.com/read/28417056/therapeutic-effect-of-prostaglandin-e1-in-monocrotaline-induced-pulmonary-arterial-hypertension-rats
#7
Jae Chul Lee
Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by sustained increase in pulmonary arterial pressure and excessive thickening and remodeling of distal small pulmonary arteries. During disease progression, PAH include increase in mean pulmonary arterial pressure, right ventricular (RV) enlargement, increased pulmonary vascular resistance, and smooth muscle hypertrophy in pulmonary arterioles. Several anti-PAH therapies targeting various pathways involved in PAH progression have been approved by the Food and Drug Adminstration...
March 2017: Anatomy & Cell Biology
https://www.readbyqxmd.com/read/28416734/the-angiotensin-receptor-blocker-losartan-inhibits-mammary-tumor-development-and-progression-to-invasive-carcinoma
#8
Rhiannon Coulson, Seng H Liew, Angela A Connelly, Nicholas S Yee, Siddhartha Deb, Beena Kumar, Ana C Vargas, Sandra A O'Toole, Adam C Parslow, Ashleigh Poh, Tracy Putoczki, Riley J Morrow, Mariah Alorro, Kyren A Lazarus, Evie F W Yeap, Kelly L Walton, Craig A Harrison, Natalie J Hannan, Amee J George, Colin D Clyne, Matthias Ernst, Andrew M Allen, Ashwini L Chand
Drugs that target the Renin-Angiotensin System (RAS) have recently come into focus for their potential utility as cancer treatments. The use of Angiotensin Receptor Blockers (ARBs) and Angiotensin-Converting Enzyme (ACE) Inhibitors (ACEIs) to manage hypertension in cancer patients is correlated with improved survival outcomes for renal, prostate, breast and small cell lung cancer. Previous studies demonstrate that the Angiotensin Receptor Type I (AT1R) is linked to breast cancer pathogenesis, with unbiased analysis of gene-expression studies identifying significant up-regulation of AGTR1, the gene encoding AT1R in ER+ve/HER2-ve tumors correlating with poor prognosis...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416592/-wnt-er-is-coming-wnt-signalling-in-chronic-lung-diseases
#9
H A Baarsma, M Königshoff
Chronic lung diseases represent a major public health problem with only limited therapeutic options. An important unmet need is to identify compounds and drugs that target key molecular pathways involved in the pathogenesis of chronic lung diseases. Over the last decade, there has been extensive interest in investigating Wingless/integrase-1 (WNT) signalling pathways; and WNT signal alterations have been linked to pulmonary disease pathogenesis and progression. Here, we comprehensively review the cumulative evidence for WNT pathway alterations in chronic lung pathologies, including idiopathic pulmonary fibrosis, pulmonary arterial hypertension, asthma and COPD...
April 17, 2017: Thorax
https://www.readbyqxmd.com/read/28416589/multimodality-imaging-of-the-tricuspid-valve-with-implication-for-percutaneous-repair-approaches
#10
REVIEW
Francesco Ancona, Stefano Stella, Maurizio Taramasso, Claudia Marini, Azeem Latib, Paolo Denti, Francesco Grigioni, Maurice Enriquez-Sarano, Ottavio Alfieri, Antonio Colombo, Francesco Maisano, Eustachio Agricola
Nowadays some percutaneous options for tricuspid valve (TV) repair are available: Tricinch (4Tech Cardio, Galway, Ireland) mimicking the Kay procedure, Trialign (Mitralign, Boston, MA, USA) aiming to bicuspidise TV, MitraClip (Abbott Vascular, Abbott Park, Illinois, USA) mimicking Alfieri's stitch, direct transcatheter annuloplasty with Cardioband (Valtech Cardio, Or Yehuda, Israel) and transcatheter Forma Repair (Edwards Lifesciences, Irvine, California, USA) providing a surface for leaflet coaptation. A multimodality imaging approach is fundamental for defining the pathophysiology of tricuspid regurgitation (TR), preprocedural planning and intraprocedural monitoring...
April 17, 2017: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/28416583/physiological-and-pathological-roles-in-human-adrenal-of-the-glomeruli-defining-matrix-protein-npnt-nephronectin
#11
Ada Ee Der Teo, Sumedha Garg, Timothy Isaac Johnson, Wanfeng Zhao, Junhua Zhou, Celso Enrique Gomez-Sanchez, Mark Gurnell, Morris Jonathan Brown
Primary aldosteronism is a common cause of hypertension, which becomes refractory if undiagnosed, but potentially curable when caused by an aldosterone-producing adenoma (APA). The discovery of somatic mutations and differences in clinical presentations led to recognition of small but common zona glomerulosa (ZG)-like adenomas, distinct from classical large zona fasciculata-like adenomas. The inverse correlation between APA size and aldosterone synthase expression prompted us to undertake a systematic study of genotype-phenotype relationships...
April 17, 2017: Hypertension
https://www.readbyqxmd.com/read/28416225/b-type-natriuretic-peptide-overexpression-ameliorates-hepatorenal-fibrocystic-disease-in%C3%A2-a%C3%A2-rat%C3%A2-model-of-polycystic-kidney-disease
#12
Sara J Holditch, Claire A Schreiber, Peter C Harris, Nicholas F LaRusso, Marina Ramirez-Alvarado, Alessandro Cataliotti, Vicente E Torres, Yasuhiro Ikeda
Polycystic kidney disease (PKD) involves progressive hepatorenal cyst expansion and fibrosis, frequently leading to end-stage renal disease. Increased vasopressin and cAMP signaling, dysregulated calcium homeostasis, and hypertension play major roles in PKD progression. The guanylyl cyclase A agonist, B-type natriuretic peptide (BNP), stimulates cGMP and shows anti-fibrotic, anti-hypertensive, and vasopressin-suppressive effects, potentially counteracting PKD pathogenesis. Here, we assessed the impacts of guanylyl cyclase A activation on PKD progression in a rat model of PKD...
April 14, 2017: Kidney International
https://www.readbyqxmd.com/read/28416132/discovery-of-indazole-aldosterone-synthase-cyp11b2-inhibitors-as-potential-treatments-for-hypertension
#13
Scott B Hoyt, Jerry Taylor, Clare London, Amjad Ali, Feroze Ujjainwalla, Jim Tata, Mary Struthers, Doris Cully, Tom Wisniewski, Ning Ren, Charlene Bopp, Andrea Sok, Andreas Verras, Daniel McMasters, Qing Chen, Elaine Tung, Wei Tang, Gino Salituro, Joe Clemas, Gaochao Zhou, Douglas MacNeil, Ruth Duffy, Yusheng Xiong
We report the discovery and hit-to-lead optimization of a structurally novel indazole series of CYP11B2 inhibitors. Benchmark compound 34 from this series displays potent inhibition of CYP11B2, high selectivity versus related steroidal and hepatic CYP targets, and lead-like physical and pharmacokinetic properties. On the basis of these and other data, the indazole series was progressed to lead optimization for further refinement.
April 8, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28415675/elevated-microrna-135a-is-associated-with-pulmonary-arterial-hypertension-in-experimental-mouse-model
#14
Hyun-Wook Lee, Sung-Hyun Park
Multiple causes are associated with the complex mechanism of pathogenesis of pulmonary arterial hypertension (PAH), but the molecular pathway in the pathogenesis of PAH is still insufficiently understood. In this study, we investigated epigenetic changes that cause PAH induced by exposure to combined Th2 antigen (Ovalbumin, OVA) and urban particulate matter (PM) in mice. To address that, we focused on the epigenetic mechanism, linked to microRNA (miR)-135a. We found that miR-135a levels were significantly increased, and levels of bone morphogenetic protein receptor type II (BMPR2) which is the target of miR-135a, were significantly decreased in this experimental PAH mouse model...
March 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415633/a-phase-2-study-of-vorinostat-in-locally-advanced-recurrent-or-metastatic-adenoid-cystic-carcinoma
#15
Priscila H Goncalves, Lance K Heilbrun, Michael T Barrett, Shivaani Kummar, Aaron R Hansen, Lillian L Siu, Richard L Piekarz, Ammar W Sukari, Joseph Chao, Mary Jo Pilat, Daryn W Smith, Lindsay Casetta, Scott A Boerner, Alice Chen, Elizabeth Lenkiewicz, Smriti Malasi, Patricia M LoRusso
PURPOSE: Vorinostat is a histone deacetylase inhibitor (HDACi). Based on a confirmed partial response (PR) in an adenoid cystic carcinoma (ACC) patient treated with vorinostat in a prior phase 1 trial, we initiated this phase 2 trial. METHODS: Vorinostat was administered orally 400 mg daily, 28 day cycles. The primary objective was to evaluate response rate (RR). Exploratory studies included whole exome sequencing (WES) of selected patients. RESULTS: Thirty patients were enrolled...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415128/p1270effects-of-blood-pressure-variability-on-layer-specific-longitudinal-strain-in-hypertension
#16
W-C Tsai, W-H Lee, Y-W Liu
Background: Our previous study showed sub-epicardial longitudinal strain (EpiLS) was an independent prognostic factor for worse outcome in regular treated hypertension but not global longitudinal strain (GLS) and sub-endocardial longitudinal strain (EndLS). Increased blood pressure variability (BPV) has been found associated with target organ damage in hypertension. However, effects of BPV on layer-specific longitudinal strain have not been well studied. Purpose: The aim of this study was to investigate the effects of different blood pressure parameters on layer-specific longitudinal strain in hypertension...
December 1, 2016: European Heart Journal Cardiovascular Imaging
https://www.readbyqxmd.com/read/28415121/p1113relationship-between-left-atrium-and-hypertensive-retinopathy-in-patients-with-systemic-hypertension-a-real-time-three-dimensional-echocardiography-based-study
#17
B Kanar, H S Kanar, A Karatay, M K Tigen
Background: The fundoscopic examination of hypertensive patients, which is an established hypertension-related target organ damage (TOD), tends to be underutilized in clinical practice. We sought to investigate the relationship between retinal alterations and left atrium (LA) volumes by means of real-time, three-dimensional echocardiography (RT3DE), which is the most pivotal predictor of diastolic dysfunction. Methods: Our population consisted of 88 consecutive essential hypertensive patients (age 59...
December 1, 2016: European Heart Journal Cardiovascular Imaging
https://www.readbyqxmd.com/read/28414064/obesity-in-coronary-heart-disease-an-unaddressed-behavioral-risk-factor
#18
Philip A Ades, Patrick D Savage
Obesity is an independent risk factor for the development and progression of coronary heart disease (CHD). Over 80% of patients with CHD are overweight or obese. While obesity is often considered a relatively "minor" CHD risk factor, weight loss is a broadly effective risk-factor intervention. Weight loss can profoundly influence a number of "major" risk factors including: hypertension, dyslipidemia and insulin resistance/type 2 diabetes mellitus. Despite its prominence as a risk factor most cardiac rehabilitation (CR) programs do not have a specific, targeted intervention to assist patients with weight loss...
April 13, 2017: Preventive Medicine
https://www.readbyqxmd.com/read/28413972/xanthine-oxidase-and-its-role-as-target-in-cardiovascular-disease-cardiovascular-protection-by-enzyme-inhibition
#19
Mirjam Schuchardt, Jaqueline Herrmann, Markus Tölle, Markus van der Giet
BACKGROUND: Formerly, hyperuricemia was mainly restricted to the rich population, but now-a-days it is a condition affecting wide parts of western civilization. Although only a minority of our population develops clinically relevant symptomatic hyperuricemia, there is growing evidence that elevated serum uric acid levels might be associated with elevated cardiovascular risk and cardiovascular disease progression. But it is not clear whether uric acid is just a biomarker or exerts detrimental effects itself...
April 17, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28413969/optimizing-the-management-of-uncontrolled-hypertension-what-do-triple-fixed-dose-drug-combinations-add
#20
Costas Thomopoulos, Georgios Katsimagklis, Stefanos Archontakis, Georgios Skalis, Thomas Makris
Fixed-dose triple drug combinations represent one of the latest innovations of pharmacotherapy for hypertension (HT). They combine a traditional renin-angiotensin system blocker, a diuretic and a calcium channel blocker. The main benefit is the simplification of treatment regimen because 3 different agents are combined at different doses in a single pill. Improving adherence to treatment partly explains why this kind of combination may effectively reduce blood pressure (BP). BP lowering by a single-pill triple-drug combination can be approximately predicted, by using appropriate formulas described in previous meta-analysis of randomized trials...
April 14, 2017: Current Vascular Pharmacology
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