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vascular remodeling and hypertension

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https://www.readbyqxmd.com/read/30098019/efficacy-of-treprostinil-in-the-su5416-hypoxia-model-of-severe-pulmonary-arterial-hypertension-hemodynamic-benefits-are-not-associated-with-improvements-in-arterial-remodelling
#1
Ketul R Chaudhary, Yupu Deng, Colin M Suen, Mohamad Taha, Thomas H Petersen, Shirley H J Mei, Duncan J Stewart
BACKGROUND AND PURPOSE: Pulmonary arterial hypertension (PAH) is a life-threatening disease that leads to progressive pulmonary hypertension, right heart failure and death. Parenteral prostaglandins, including treprostinil, a prostacyclin analogue, represent the most effective medical treatment for severe PAH. We investigated the effect of treprostinil on established severe PAH and underlying mechanisms using the rat SU5416 (SU, a vascular endothelial growth factor receptor-2 inhibitor)-chronic hypoxia (Hx) model of PAH...
August 11, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/30093868/inositol-1-4-5-trisphosphate-receptors-in-hypertension
#2
REVIEW
Ali H Eid, Ahmed F El-Yazbi, Fouad Zouein, Abdelilah Arredouani, Allal Ouhtit, Md M Rahman, Hatem Zayed, Gianfranco Pintus, Haissam Abou-Saleh
Chronic hypertension remains a major cause of global mortality and morbidity. It is a complex disease that is the clinical manifestation of multiple genetic, environmental, nutritional, hormonal, and aging-related disorders. Evidence supports a role for vascular aging in the development of hypertension involving an impairment in endothelial function together with an alteration in vascular smooth muscle cells (VSMCs) calcium homeostasis leading to increased myogenic tone. Changes in free intracellular calcium levels ([Ca2+ ] i ) are mediated either by the influx of Ca2+ from the extracellular space or release of Ca2+ from intracellular stores, mainly the sarcoplasmic reticulum (SR)...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/30091406/role-of-nlrp-3-inflammasome-in-hypertension-a-potential-therapeutic-target
#3
Teresa Pasqua, Pasquale Pagliaro, Carmine Rocca, Tommaso Angelone, Claudia Penna
Background Hypertension is a multifactorial and chronic cardiovascular condition whose complications are responsible for worldwide morbidity and mortality. An increasing body of experimental data, recognize low-grade inflammation as a basic process in hypertension onset and development since there is a strong contribution of both the innate and the adaptive immune system according to the so-called Danger-Model. In this contest, NLRP3 inflammasome represents a key signaling platform as demonstrated by its implication in several hypertension-associated conditions, such as vascular smooth muscle remodeling and proliferation...
August 8, 2018: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/30091380/sodium-nitrite-augments-lung-s-nitrosylation-and-reverses-chronic-hypoxic-pulmonary-hypertension-in-juvenile-rats
#4
Robert P Jankov, Kathrine Louise Daniel, Shira Iny, Crystal Kantores, Julijana Ivanovska, Naya Ben Fadel, Amish Jain
Deficient nitric oxide (NO) signaling plays a critical role in the pathogenesis of chronic neonatal pulmonary hypertension (PHT). Physiological NO signaling is regulated by S-nitrosothiols (SNOs), which act both as a reservoir for NO and as a reversible modulator of protein function. We have previously reported that therapy with inhaled NO (iNO) increased peroxynitrite-mediated nitration in the juvenile rat lung, while having minimal reversing effects on vascular remodeling. We hypothesized that sodium nitrite (NaNO2) would be superior to iNO in enhancing lung SNOs, thereby contributing to reversal of chronic hypoxic PHT...
August 9, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/30090065/mechanobiological-feedback-in-pulmonary-vascular-disease
#5
REVIEW
Paul B Dieffenbach, Marcy Maracle, Daniel J Tschumperlin, Laura E Fredenburgh
Vascular stiffening in the pulmonary arterial bed is increasingly recognized as an early disease marker and contributor to right ventricular workload in pulmonary hypertension. Changes in pulmonary artery stiffness throughout the pulmonary vascular tree lead to physiologic alterations in pressure and flow characteristics that may contribute to disease progression. These findings have led to a greater focus on the potential contributions of extracellular matrix remodeling and mechanical signaling to pulmonary hypertension pathogenesis...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/30087110/rna-editing-of-filamin-a-pre-mrna-regulates-vascular-contraction-and-diastolic-blood-pressure
#6
Mamta Jain, Tomer D Mann, Maja Stulić, Shailaja P Rao, Andrijana Kirsch, Dieter Pullirsch, Xué Strobl, Claus Rath, Lukas Reissig, Kristin Moreth, Tanja Klein-Rodewald, Raffi Bekeredjian, Valerie Gailus-Durner, Helmut Fuchs, Martin Hrabě de Angelis, Eleonore Pablik, Laura Cimatti, David Martin, Jelena Zinnanti, Wolfgang F Graier, Maria Sibilia, Saša Frank, Erez Y Levanon, Michael F Jantsch
Epitranscriptomic events such as adenosine-to-inosine (A-to-I) RNA editing by ADAR can recode mRNAs to translate novel proteins. Editing of the mRNA that encodes actin crosslinking protein Filamin A (FLNA) mediates a Q-to-R transition in the interactive C-terminal region. While FLNA editing is conserved among vertebrates, its physiological function remains unclear. Here, we show that cardiovascular tissues in humans and mice show massive editing and that FLNA RNA is the most prominent substrate. Patient-derived RNA-Seq data demonstrate a significant drop in FLNA editing associated with cardiovascular diseases...
August 7, 2018: EMBO Journal
https://www.readbyqxmd.com/read/30081553/factors-associated-with-heritable-pulmonary-arterial-hypertension-exert-convergent-actions-on-the-mir-130-301-vascular-matrix-feedback-loop
#7
Thomas Bertero, Adam L Handen, Stephen Y Chan
Pulmonary arterial hypertension (PAH) is characterized by occlusion of lung arterioles, leading to marked increases in pulmonary vascular resistance. Although heritable forms of PAH are known to be driven by genetic mutations that share some commonality of function, the extent to which these effectors converge to regulate shared processes in this disease is unknown. We have causally connected extracellular matrix (ECM) remodeling and mechanotransduction to the miR-130/301 family in a feedback loop that drives vascular activation and downstream PAH...
August 4, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/30081463/myeloid-derived-suppressor-cells-and-pulmonary-hypertension
#8
REVIEW
Andrew J Bryant, Borna Mehrad, Todd M Brusko, James D West, Lyle L Moldawer
Myeloid⁻derived suppressor cells (MDSCs) comprised a heterogeneous subset of bone marrow⁻derived myeloid cells, best studied in cancer research, that are increasingly implicated in the pathogenesis of pulmonary vascular remodeling and the development of pulmonary hypertension. Stem cell transplantation represents one extreme interventional strategy for ablating the myeloid compartment but poses a number of translational challenges. There remains an outstanding need for additional therapeutic targets to impact MDSC function, including the potential to alter interactions with innate and adaptive immune subsets, or alternatively, alter trafficking receptors, metabolic pathways, and transcription factor signaling with readily available and safe drugs...
August 3, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/30078284/-characteristics-of-pulmonary-vascular-remodeling-in-rat-model-of-pulmonary-hypertension-in-left-heart-disease
#9
H Zhang, H J Liu, W H Huang, L W Chen
Objective: To investigate pulmonary vascular remodeling in rat model of pulmonary hypertension in left heart disease (PH-LHD). Methods: A total of 66 male minor Sprague-Dawley (SD) rats were randomly divided into control group ( n =6), sham operation group ( n =6) and model group ( n =54). The rats in the control group entered the experimental procedure immediately without any treatment, and the rats in the sham operation group entered the experimental procedure 64 days after sham operation, and the rats in model group entered the experimental procedure (6 rats each) on day 1, day 3, day 5, day 8, day 15, day 22, day 36, day 50 and day 64 respectively after supracoronary aortic banding successfully...
July 24, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/30078229/berberine-attenuates-pulmonary-arterial-hypertension-via-protein-phosphatase-2a-signaling-pathway-both-in-vivo-and-in-vitro
#10
Jie Luo, Yue Gu, Pengfei Liu, Xiaomin Jiang, Wande Yu, Peng Ye, Yuelin Chao, Hongfeng Yang, Linlin Zhu, Ling Zhou, Shaoliang Chen
Excessive proliferation, migration, and antiapoptosis of pulmonary artery (PA) smooth muscle cells (PASMCs) underlies the development of pulmonary vascular remodeling. The innervation of the PA is predominantly sympathetic, and increased levels of circulating catecholamines have been detected in pulmonary arterial hypertension (PAH), suggesting that neurotransmitters released by sympathetic overactivation may play an essential role in PAH. However, the responsible mechanism remains unclear. Here, to investigate the effects of norepinephrine (NE) on PASMCs and the related mechanism, we used 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, the proliferating cell nuclear antigen and the cell counting kit-8 assay to evaluate the proliferation of PASMCs, Boyden chamber migration, and wound-healing assays to assess migration and western blot analysis to investigate protein expression...
August 5, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/30073166/pulmonary-arterial-stiffness-an-early-and-pervasive-driver-of-pulmonary-arterial-hypertension
#11
REVIEW
Wei Sun, Stephen Y Chan
Pulmonary arterial hypertension (PAH) is a historically neglected and highly morbid vascular disease that leads to right heart failure and, in some cases, death. The molecular origins of this disease have been poorly defined, and as such, current pulmonary vasodilator therapies do not cure or reverse this disease. Although extracellular matrix (ECM) remodeling and pulmonary arterial stiffening have long been associated with end-stage PAH, recent studies have reported that such vascular stiffening can occur early in pathogenesis...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/30067297/long-term-pulmonary-vascular-consequences-of-perinatal-insults
#12
Kara Goss
Development of the pulmonary circulation is a critical component of fetal lung development, and continues throughout infancy and childhood, marking an extended window of susceptibility to vascular maldevelopment and maladaptation. Perinatal vascular insults may result in abnormal vascular structure or function, including decreased angiogenic signaling and vascular endowment, impaired vasoreactivity through increased pulmonary artery endothelial dysfunction and remodeling, or enhanced genetic susceptibility to pulmonary vascular disease through epigenetic modifications or germline mutations...
August 1, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/30060976/changes-in-the-choroid-plexuses-and-brain-barriers-associated-with-high-blood-pressure-and-ageing
#13
I Gonzalez-Marrero, L G Hernández-Abad, L Castañeyra-Ruiz, E M Carmona-Calero, A Castañeyra-Perdomo
INTRODUCTION: The choroid plexuses, blood vessels, and brain barriers are closely related both in terms of morphology and function. Hypertension causes changes in cerebral blood flow and in small vessels and capillaries of the brain. This review studies the effects of high blood pressure (HBP) on the choroid plexuses and brain barriers. DEVELOPMENT: The choroid plexuses (ChP) are structures located in the cerebral ventricles, and are highly conserved both phylogenetically and ontogenetically...
July 27, 2018: Neurología: Publicación Oficial de la Sociedad Española de Neurología
https://www.readbyqxmd.com/read/30055414/the-combination-of-maternal-kir-b-and-fetal-hla-c2-is-associated-with-decidua-basalis-acute-atherosis-in-pregnancies-with-preeclampsia
#14
Guro M Johnsen, Gro L Størvold, Jos J M Drabbels, Geert W Haasnoot, Michael Eikmans, Marijke J Spruyt-Gerritse, Patji Alnæs-Katjavivi, Sicco A Scherjon, Christopher W G Redman, Frans H J Claas, Anne Cathrine Staff
Acute atherosis is an arterial lesion most often occurring in pregnancies complicated by preeclampsia, a hypertensive pregnancy disorder. Acute atherosis predominates in the maternal spiral arteries in the decidua basalis layer of the pregnant uterus. This layer forms the fetal-maternal immunological interface, where fetal extravillous trophoblasts interact with maternal immune cells to promote decidual spiral artery remodeling and maternal immune tolerance towards the fetus. Of the classical polymorphic class I HLAs, extravillous trophoblasts express only HLA-C...
July 25, 2018: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/30053410/paeonol-regulates-hypoxia-induced-proliferation-of-pulmonary-artery-smooth-muscle-cells-via-ekr-1-2-signaling
#15
Lixin Zhang, Cui Ma, Rui Gu, Min Zhang, Xiaoying Wang, Lin Yang, Ying Liu, Yutian Zhou, Siyu He, Daling Zhu
Pulmonary hypertension (PH) is a disease with a developmental origin characterized by obstructive vascular remodelling that is partially due to excessive pulmonary arterial smooth muscle cells (PASMCs) proliferation. Paeonol has important effects on vascular cell proliferation, migration, and inflammation, but researchers have not determined whether paeonol participates in the development and progression of pulmonary vascular remodelling. We explored the remarkable anti-proliferative effects of paeonol on hypoxic PASMCs, which are postulated to be mediated by the extracellular signal-regulated kinase 1 and 2 (ERK1/2) signalling pathway...
July 24, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/30051404/the-role-of-sex-in-the-pathophysiology-of-pulmonary-hypertension
#16
Craig K Docherty, Katie Yates Harvey, Kirsty M Mair, Sinead Griffin, Nina Denver, Margaret R MacLean
Pulmonary arterial hypertension (PAH) is a progressive disease characterised by increased pulmonary vascular resistance and pulmonary artery remodelling as result of increased vascular tone and vascular cell proliferation, respectively. Eventually, this leads to right heart failure. Heritable PAH is caused by a mutation in the bone morphogenetic protein receptor-II (BMPR-II). Female susceptibility to PAH has been known for some time, and most recent figures show a female-to-male ratio of 4:1. Variations in the female sex hormone estrogen and estrogen metabolism modify FPAH risk, and penetrance of the disease in BMPR-II mutation carriers is increased in females...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/30051401/cardiovascular-sequels-during-and-after-preeclampsia
#17
Nina D Paauw, A Titia Lely
Preeclampsia is a pregnancy-specific disorder complicating 2%-8% of pregnancies worldwide and characterized by de novo development of hypertension and proteinuria. Current understanding of the pathophysiology of preeclampsia is limited. A main feature is disrupted spiral artery remodeling in the placenta, which restricts the blood flow to the placenta, which in turn leads to decreased uteroplacental perfusion. Impaired blood flow through the placenta might result in fetal growth restriction and secretion of several factors by the placenta-mainly pro-inflammatory cytokines and anti-angiogenic factors-which spread into the maternal circulation, leading to endothelial dysfunction, which subsequently results in disrupted maternal hemodynamics...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/30050455/reactive-oxygen-species-and-pulmonary-vasculature-during-hypobaric-hypoxia
#18
REVIEW
Patricia Siques, Julio Brito, Eduardo Pena
An increasing number of people are living or working at high altitudes (hypobaric hypoxia) and therefore suffering several physiological, biochemical, and molecular changes. Pulmonary vasculature is one of the main and first responses to hypoxia. These responses imply hypoxic pulmonary vasoconstriction (HPV), remodeling, and eventually pulmonary hypertension (PH). These events occur according to the type and extension of the exposure. There is also increasing evidence that these changes in the pulmonary vascular bed could be mainly attributed to a homeostatic imbalance as a result of increased levels of reactive oxygen species (ROS)...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/30045361/mechanical-pressure-unloading-therapy-reverses-thoracic-aortic-structural-and-functional-changes-in-a-hypertensive-rat-model
#19
Sevil Korkmaz-Icöz, Paige Brlecic, Mihály Ruppert, Tamás Radovits, Matthias Karck, Gábor Szabó
OBJECTIVES: Hypertension can impair structure and function of blood vessels. Experimental data describing the reverse remodeling process after a mechanical pressure unloading therapy in the vasculature is limited. We studied the influence of pressure unloading on both the structural and functional alterations of the aorta in a hypertensive rat model. METHODS: Using isolated thoracic aortic rings in an in-vitro organ bath system, endothelium-dependent and endothelium-independent vasorelaxation were studied 6-weeks or 12-weeks after abdominal aortic banding (aortic banding-6-week or aortic banding-12-week), and 6-weeks after an aortic debanding procedure performed after the sixth experimental week of aortic banding (aortic banding + debanding-12-week)...
July 24, 2018: Journal of Hypertension
https://www.readbyqxmd.com/read/30044141/stabilization-of-p22phox-by-hypoxia-promotes-pulmonary-hypertension
#20
Andreas Petry, Benjamin Trautz, Damir Kracun, Zuwen Zhang, Frederick Vogel, Michael Weitnauer, Katharina Hochkogler, Agnes Görlach
BACKGROUND: Hypoxia and reactive oxygen species (ROS) have been shown to play a role in the pathogenesis of pulmonary hypertension, a potentially fatal disorder characterized by pulmonary vascular remodeling, elevated pulmonary arterial pressure and right ventricular hypertrophy. However, how they are linked in the context of pulmonary hypertension is not completely understood. AIMS: We therefore investigated the role of the NADPH oxidase subunit p22phox,in the response to hypoxia in vitro and in vivo...
July 25, 2018: Antioxidants & Redox Signaling
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