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https://www.readbyqxmd.com/read/28805015/stromelysin-2-mmp-10-a-novel-mediator-of-vascular-remodeling-underlying-pulmonary-hypertension-associated-with-systemic-sclerosis
#1
Jérôme Avouac, Christophe Guignabert, Anna Maria Hoffmann-Vold, Barbara Ruiz, Peter Dorfmuller, Sonia Pezet, Olivia Amar, Ly Tu, Jérôme Van Wassenhove, Jérémy Sadoine, David Launay, Muriel Elhai, Anne Cauvet, Arun Subramaniam, Robert Resnick, Eric Hachulla, Øyvind Molberg, André Kahan, Marc Humbert, Yannick Allanore
OBJECTIVE: To decipher the role of gene candidates involved in pulmonary hypertension (PH) associated with systemic sclerosis (SSc). METHODS: Gene candidates were identified through microarray experiments performed on Affymetrix GeneChip(®) Human Exon 1.0 ST Arrays in endothelial progenitor cell (EPC)-derived endothelial cells (ECs) issued from patients with SSc-PH, SSc without PH and controls. Expression of identified candidates was assessed by quantitative sandwich ELISA in the serum and by immunohistochemistry in lesional lung tissue...
August 13, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28801346/pan-ppar-agonist-iva337-is-effective-in-experimental-lung-fibrosis-and-pulmonary-hypertension
#2
Jerome Avouac, Irena Konstantinova, Christophe Guignabert, Sonia Pezet, Jeremy Sadoine, Thomas Guilbert, Anne Cauvet, Ly Tu, Jean-Michel Luccarini, Jean-Louis Junien, Pierre Broqua, Yannick Allanore
OBJECTIVE: To evaluate the antifibrotic effects of the pan-peroxisome proliferator-activated receptor (PPAR) agonist IVA337 in preclinical mouse models of pulmonary fibrosis and related pulmonary hypertension (PH). METHODS: IVA337 has been evaluated in the mouse model of bleomycin-induced pulmonary fibrosis and in Fra-2 transgenic mice, this latter being characterised by non-specific interstitial pneumonia and severe vascular remodelling of pulmonary arteries leading to PH...
August 11, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28801243/peroxiredoxin-2-plays-a-pivotal-role-as-multimodal-cytoprotector-in-the-early-phase-of-pulmonary-hypertension
#3
Enrica Federti, Alessandro Matte', Alessandra Ghigo, Immacolata Andolfo, Cimino James, Angela Siciliano, Christophe Leboeuf, Anne Janin, Francesco Manna, Soo Young Choi, Achille Iolascon, Elisabetta Beneduce, Davide Melisi, Dae Won Kim, Sonia Levi, Lucia De Franceschi
Pulmonary-artery-hypertension (PAH) is a life-threatening and highly invalidating chronic disorder. Chronic oxidation contributes to lung damage and disease progression. Peroxiredoxin-2 (Prx2) is a typical 2-cysteine (Cys) peroxiredoxin but its role on lung homestasis is yet to be fully defined. Here, we showed that Prx2(-/-) mice displayed chronic lung inflammatory disease associated with (i) abnormal pulmonary vascular dysfunction; and (ii) increased markers of extracellular-matrix remodeling. Hypoxia was used to induce PAH...
August 8, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28800253/targeting-pulmonary-endothelial-hemoglobin-%C3%AE-improves-nitric-oxide-signaling-and-reverses-pulmonary-artery-endothelial-dysfunction
#4
Roger A Alvarez, Megan P Miller, Scott A Hahn, Joseph C Galley, Eileen Bauer, Timothy Bachman, Jian Hu, John Sembrat, Dmitry Goncharov, Ana L Mora, Mauricio Rojas, Elena Goncharova, Adam C Straub
RATIONALE: Pulmonary hypertension is characterized by pulmonary endothelial dysfunction. Previous work showed that systemic artery endothelial cells express hemoglobin α to control nitric oxide diffusion, but the role of this system in the pulmonary circulation has not been evaluated. OBJECTIVES: We hypothesize that up-regulation of hemoglobin α in pulmonary endothelial cells contributes to nitric oxide depletion and pulmonary vascular dysfunction in pulmonary hypertension...
August 11, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28798540/growth-differentiation-factor-15-may-predict-mortality-of-peripheral-and-coronary-artery-diseases-and-correlate-with-their-risk-factors
#5
Lung-An Hsu, Semon Wu, Jyh-Ming Jimmy Juang, Fu-Tien Chiang, Ming-Sheng Teng, Jeng-Feng Lin, Hsuan-Li Huang, Yu-Lin Ko
Plasma GDF15 concentrations were measured in 612 Taiwanese individuals without overt systemic disease. Clinical parameters, GDF15 genetic variants, and 22 biomarker levels were analyzed. We further enrolled 86 patients with PAD and 481 patients with CAD, who received endovascular intervention and coronary angiography, respectively, to examine the role of GDF15 level in predicting all-cause mortality. Significant associations were found between GDF15 genotypes/haplotypes and GDF15 levels. The circulating GDF15 level was positively associated with age, smoking, hypertension, and diabetes mellitus as well as circulating levels of lipocalin 2 and various biomarkers of inflammation and oxidative stress...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28798259/endothelial-cell-related-autophagic-pathways-in-sugen-hypoxia-exposed-pulmonary-arterial-hypertensive-rats
#6
Fumiaki Kato, Seiichiro Sakao, Takao Takeuchi, Toshio Suzuki, Rintaro Nishimura, Tadashi Yasuda, Nobuhiro Tanabe, Koichiro Tatsumi
Pulmonary arterial hypertension (PAH) is characterized by progressive obstructive remodeling of pulmonary arteries. However, no reports have described the causative role of the autophagic pathway in pulmonary vascular endothelial cell (EC) alterations associated with PAH. This study investigated the time-dependent role of the autophagic pathway in pulmonary vascular ECs and pulmonary vascular EC kinesis in a severe PAH rat model (Sugen/Hypoxia rat) and evaluated whether timely induction of the autophagic pathway by rapamycin improves PAH...
August 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28798201/remote-ischemic-preconditioning-does-not-prevent-acute-mountain-sickness-after-rapid-ascent-to-3450-m
#7
Marc M Berger, Franziska Macholz, Lukas Lehmann, Daniel Dankl, Marcel Hochreiter, Bernhard Bacher, Peter Bärtsch, Heimo Mairbäurl
Remote ischemic preconditioning (RIPC) has been shown to protect remote organs, such as the brain and the lung, from damage induced by subsequent hypoxia or ischemia. Acute mountain sickness (AMS) is a syndrome of non-specific neurologic symptoms and in high altitude pulmonary edema excessive hypoxic pulmonary vasoconstriction (HPV) plays a pivotal role. We hypothesized that RIPC protects the brain from AMS and attenuates the magnitude of HPV after rapid ascent to 3450 m. Forty non-acclimatized volunteers were randomized into 2 groups...
August 10, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28796632/the-association-of-arsenic-metabolism-with-cancer-cardiovascular-disease-and-diabetes-a-systematic-review-of-the-epidemiological-evidence
#8
Chin-Chi Kuo, Katherine A Moon, Shu-Li Wang, Ellen Silbergeld, Ana Navas-Acien
BACKGROUND: The available evidence on the role of arsenic metabolism in individual susceptibility to the development of cancer, cardiovascular disease, and diabetes has not been formally and comprehensively reviewed. OBJECTIVES: Our goal was to systematically investigate the association of arsenic metabolism with cancer, cardiovascular disease, and diabetes-related outcomes in epidemiologic studies. As a secondary objective, we characterized the variation of arsenic metabolism in different populations worldwide...
August 1, 2017: Environmental Health Perspectives
https://www.readbyqxmd.com/read/28794356/early-onset-severe-chronic-obstructive-pulmonary-disease-with-pulmonary-hypertension-that-was-likely-induced-by-toluene-exposure
#9
Konomi Kobayashi, Manabu Suzuki, Shota Yamamoto, Keisuke Ueno, Eriko Miyawaki, Ikuo Takazawa, Ayako Shiozawa, Teruhiko Sato, Masayuki Hojo, Haruhito Sugiyama
Early-onset pulmonary emphysema is uncommon and its pathogenesis is poorly defined. A 30-year-old man was admitted to our intensive care unit with severe respiratory failure. Besides smoking heavily since the 14 years of age, he had habitually inhaled organic solvents, such as toluene, in his adolescence. High-resolution computed tomography showed evident pulmonary emphysema throughout the lung fields. Based on the findings of right heart catheterization, he was diagnosed with an acute exacerbation of chronic obstructive pulmonary disease complicated with pulmonary hypertension...
August 10, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28792962/aberrant-cgmp-signaling-persists-during-recovery-in-mice-with-oxygen-induced-pulmonary-hypertension
#10
Marta Perez, Keng Jin Lee, Herminio J Cardona, Joann M Taylor, Mary E Robbins, Gregory B Waypa, Sara K Berkelhamer, Kathryn N Farrow
Bronchopulmonary dysplasia (BPD), a common complication of preterm birth, is associated with pulmonary hypertension (PH) in 25% of infants with moderate to severe BPD. Neonatal mice exposed to hyperoxia for 14d develop lung disease similar to BPD, with evidence of associated PH. The cyclic guanosine monophosphate (cGMP) signaling pathway has not been well studied in BPD-associated PH. In addition, there is little data about the natural history of hyperoxia-induced PH in mice or the utility of phosphodiesterase-5 (PDE5) inhibition in established disease...
2017: PloS One
https://www.readbyqxmd.com/read/28790817/emerging-pharmaceutical-therapies-for-copd
#11
REVIEW
Sowmya P Lakshmi, Aravind T Reddy, Raju C Reddy
COPD, for which cigarette smoking is the major risk factor, remains a worldwide burden. Current therapies provide only limited short-term benefit and fail to halt progression. A variety of potential therapeutic targets are currently being investigated, including COPD-related proinflammatory mediators and signaling pathways. Other investigational compounds target specific aspects or complications of COPD such as mucus hypersecretion and pulmonary hypertension. Although many candidate therapies have shown no significant effects, other emerging therapies have improved lung function, pulmonary hypertension, glucocorticoid sensitivity, and/or the frequency of exacerbations...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28790516/the-molecular-basis-of-portal-hypertension
#12
Don C Rockey
Cirrhosis leads to portal hypertension and vascular abnormalities in multiple vascular beds. There is intense vasoconstriction in the liver and the kidneys, but also vasodilation in the other vascular beds, including the periphery, lungs, brain, and mesentery. The derangement in each of these beds leads to specific clinical disease. The vasoconstrictive phenotype in the liver ultimately leads to clinical portal hypertension, and is caused by an imbalance of vasoconstrictive and vasorelaxing molecules, which will be the focus of this review...
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28790293/-critical-care-managements-after-lung-transplantation
#13
Masaki Anraku
Lung transplantation is a viable treatment option for patients with end-stage lung diseases such as interstitial pneumonia/pulmonary fibrosis, emphysema, pulmonary hypertension, and so on. Collecting available clinical, physiological, serological, and surgical information of both donor and recipient is vital when planning relevant postoperative managements. The goal of the managements is to keep the transplanted lung (s) functional while preventing/treating infection, rejection, and ischemiareperfusion lung injury...
July 2017: Kyobu Geka. the Japanese Journal of Thoracic Surgery
https://www.readbyqxmd.com/read/28789830/sphingosine-kinase-1-a-potential-therapeutic-target-in-pulmonary-arterial-hypertension
#14
REVIEW
Nigel J Pyne, Susan Pyne
Sphingosine kinase 1 (SphK1) knockout mice are protected against pulmonary hypertension and expression levels of the enzyme are increased in the lungs of pulmonary arterial hypertensive (PAH) patients. Moreover, sphingosine 1-phosphate can promote vascular remodeling/vasoconstriction in rodent and human pulmonary arterial smooth muscle cell models. Therefore, SphK1 might be a novel target for treatment of PAH. However, in our opinion, more refined strategies to target SphK1 are needed because this enzyme is protective against endothelial dysfunction and can become resistant to SphK1 inhibitors in vascular smooth muscle, thereby potentially limiting their effectiveness in PAH...
August 5, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28782710/use-of-nebulized-milrinone-in-cardiac-surgery-comparison-of-vibrating-mesh-and-simple-jet-nebulizers
#15
Paul Gavra, Maxime Laflamme, André Y Denault, Yves Théôret, Louis P Perrault, France Varin
Cardiopulmonary bypass triggers an ischemia-reperfusion injury with endothelial dysfunction in the pulmonary circulation which can result in pulmonary hypertension. Inhaled milrinone reduces this reperfusion phenomenon and two methods commonly available for administering it are simple jet and vibrating mesh nebulization. However, neither their generated milrinone particle size profiles, nor their ability to aid endothelial relaxation have been compared. Simple jet and vibrating mesh particle size distributions of milrinone were verified through cascade impaction and their efficacy was tested on a cardiopulmonary bypass (CPB) swine model...
August 4, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28782495/rapidly-progressive-pulmonary-veno-occlusive-disease-in-an-infant-with-down-syndrome
#16
Jun Muneuchi, Shinichiro Oda, Daisuke Shimizu
A 4-month-old girl with Down syndrome showed unexpected deterioration of pulmonary hypertension. Despite aggressive pulmonary vasodilation therapy, the patient died at 5 months of age. Lung autopsy showed that the pulmonary veins were obliterated by intimal fibrous thickening, and the media of the veins was arterialised with an increase in elastic fibres. Pulmonary veno-occlusive disease should be considered in the management of individuals with Down syndrome.
September 2017: Cardiology in the Young
https://www.readbyqxmd.com/read/28776262/visceral-adipose-tissue-derived-serine-protease-inhibitor-prevents-the-development-of-monocrotaline-induced-pulmonary-arterial-hypertension-in-rats
#17
Yuzaburo Sakamoto, Satoshi Kameshima, Chiharu Kakuda, Yuta Okamura, Tomoko Kodama, Muneyoshi Okada, Hideyuki Yamawaki
Visceral adipose tissue-derived serine protease inhibitor (vaspin), a recently identified adipocytokine, inhibits inflammation, migration, and apoptosis of vascular cells. We have recently demonstrated that chronic administration of vaspin to spontaneously hypertensive rats partly prevents systemic hypertension through inhibiting inflammation and remodeling of vascular wall. Pulmonary arterial (PA) hypertension (PAH) is caused by PA remodeling, contractile dysfunction, and inflammatory responses. We tested the hypothesis that vaspin could prevent development of PAH in animal model...
August 3, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28775095/transglutaminase-2-in-pulmonary-and-cardiac-tissue-remodeling-in-experimental-pulmonary-hypertension
#18
Krishna C Penumatsa, Deniz Toksoz, Rod R Warburton, Mousa Kharnaf, Ioana R Preston, Navin Kumar Kapur, Chaitan Khosla, Nicholas S Hill, Barry L Fanburg
Tissue matrix remodeling and fibrosis leading to loss of pulmonary arterial and right ventricular compliance are important features of both experimental and clinical pulmonary hypertension (PH). We have previously reported that transglutaminase 2 (TG2) is involved in PH development while others have shown it to be a crosslinking enzyme that participates in remodeling of extracellular matrix in fibrotic diseases in general. In the present studies, we used a mouse model of experimental PH (Sugen 5416 and hypoxia; SuHypoxia) and cultured primary human cardiac and pulmonary artery adventitial fibroblasts to evaluate the relationship of TG2 to the processes of fibrosis, protein crosslinking, extracellular matrix collagen accumulation and fibroblast to myofibroblast transformation...
August 3, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28775050/risk-assessment-prognosis-and-guideline-implementation-in-pulmonary-arterial-hypertension
#19
Athénaïs Boucly, Jason Weatherald, Laurent Savale, Xavier Jaïs, Vincent Cottin, Grégoire Prevot, François Picard, Pascal de Groote, Mitja Jevnikar, Emmanuel Bergot, Ari Chaouat, Céline Chabanne, Arnaud Bourdin, Florence Parent, David Montani, Gérald Simonneau, Marc Humbert, Olivier Sitbon
Current European guidelines recommend periodic risk assessment for patients with pulmonary arterial hypertension (PAH). The aim of our study was to determine the association between the number of low-risk criteria achieved within 1 year of diagnosis and long-term prognosis.Incident patients with idiopathic, heritable and drug-induced PAH between 2006 and 2016 were analysed. The number of low-risk criteria present at diagnosis and at first re-evaluation were assessed: World Health Organization (WHO)/New York Heart Association (NYHA) functional class I or II, 6-min walking distance (6MWD) >440 m, right atrial pressure <8 mmHg and cardiac index ≥2...
August 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28774463/clinical-trials-a-pending-subject
#20
B Gil-Extremera, P Jiménez-López, J D Mediavilla-García
Clinical trials are essential tools for the progress of clinical medicine in its diagnostic and therapeutic aspects. Since the first trial in 1948, which related tobacco use with lung cancer, there have been more than 150,000 clinical trials to date in various areas (paediatrics, cardiology, oncology, endocrinology, etc.). This article highlights the importance for all physicians to participate, over the course of their professional career, in a clinical trial, due to the inherent benefits for patients, the progress of medicine and for curricular prestige...
July 31, 2017: Revista Clínica Española
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