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Pulmonary endothelium

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https://www.readbyqxmd.com/read/28337251/pentaerythritol-tetranitrate-in-vivo-treatment-improves-oxidative-stress-and-vascular-dysfunction-by-suppression-of-endothelin-1-signaling-in-monocrotaline-induced-pulmonary-hypertension
#1
Sebastian Steven, Matthias Oelze, Moritz Brandt, Elisabeth Ullmann, Swenja Kröller-Schön, Tjebo Heeren, Lan P Tran, Steffen Daub, Mobin Dib, Dirk Stalleicken, Philip Wenzel, Thomas Münzel, Andreas Daiber
Objective. Oxidative stress and endothelial dysfunction contribute to pulmonary arterial hypertension (PAH). The role of the nitrovasodilator pentaerythritol tetranitrate (PETN) on endothelial function and oxidative stress in PAH has not yet been defined. Methods and Results. PAH was induced by monocrotaline (MCT, i.v.) in Wistar rats. Low (30 mg/kg; MCT30), middle (40 mg/kg; MCT40), or high (60 mg/kg; MCT60) dose of MCT for 14, 28, and 42 d was used. MCT induced endothelial dysfunction, pulmonary vascular wall thickening, and fibrosis, as well as protein tyrosine nitration...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28306336/fifty-years-of-research-in-ards-cell-based-therapy-for-ards-biology-and-potential-therapeutic-value
#2
John G Laffey, Michael A Matthay
Based on several pre-clinical studies, cell-based therapy has emerged as a potential new therapeutic for ARDS. Of the various cell-based therapy options, mesenchymal stromal cells (MSCs) from bone marrow, adipose tissue and umbilical cord have the most experimental data to support their potential efficacy for lung injury from both infectious and non-infectious causes. Mechanistically, MSCs exert their beneficial effects by release of paracrine factors, microvesicles, and transfer of mitochondria, all of which have anti-inflammatory and pro-resolving effects on injured lung endothelium and alveolar epithelium, including enhancing the resolution of pulmonary edema by upregulating sodium-dependent alveolar fluid clearance...
March 17, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28304180/nanomedicine-for-the-treatment-of-acute-respiratory-distress-syndrome-the-2016-ats-bear-cage-award-winning-proposal
#3
Jacob S Brenner
After dozens of clinical trials, there are still no FDA-approved drugs which improve mortality in acute respiratory distress syndrome (ARDS). These poor results may in part be caused by three unique pharmacological challenges presented by ARDS: 1) ARDS patients are fragile due to concomitant multiple organ dysfunction, so do not tolerate off-target side effects of drugs; 2) inhaled drug delivery is impeded by the column of proteinaceous fluid covering the injured alveoli; 3) ARDS is heterogeneous in its underlying pathophysiology, so targeting one pathway is unlikely to improve most patients...
March 17, 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28293165/-pyr-1-apelin-13-1-12-is-a-biologically-active-ace2-metabolite-of-the-endogenous-cardiovascular-peptide-pyr-1-apelin-13
#4
Peiran Yang, Rhoda E Kuc, Aimée L Brame, Alex Dyson, Mervyn Singer, Robert C Glen, Joseph Cheriyan, Ian B Wilkinson, Anthony P Davenport, Janet J Maguire
Aims: Apelin is a predicted substrate for ACE2, a novel therapeutic target. Our aim was to demonstrate the endogenous presence of the putative ACE2 product [Pyr(1)]apelin-13(1-12) in human cardiovascular tissues and to confirm it retains significant biological activity for the apelin receptor in vitro and in vivo. The minimum active apelin fragment was also investigated. Methods and Results: [Pyr(1)]apelin-13 incubated with recombinant human ACE2 resulted in de novo generation of [Pyr(1)]apelin-13(1-12) identified by mass spectrometry...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28287530/open-tracheostomy-gastric-acid-aspiration-murine-model-of-acute-lung-injury-results-in-maximal-acute-nonlethal-lung-injury
#5
Ravi Alluri, Hilliard L Kutscher, Barbara A Mullan, Bruce A Davidson, Paul R Knight
Acid pneumonitis is a major cause of sterile acute lung injury (ALI) in humans. Acid pneumonitis spans the clinical spectrum from asymptomatic to acute respiratory distress syndrome (ARDS), characterized by neutrophilic alveolitis, and injury to both alveolar epithelium and vascular endothelium. Clinically, ARDS is defined by acute onset of hypoxemia, bilateral patchy pulmonary infiltrates and non-cardiogenic pulmonary edema. Human studies have provided us with valuable information about the physiological and inflammatory changes in the lung caused by ARDS, which has led to various hypotheses about the underling mechanisms...
February 26, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28277743/obesity-induced-endoplasmic-reticulum-stress-causes-lung-endothelial-dysfunction-and-promotes-acute-lung-injury
#6
Dilip Shah, Freddy Romero, Zhi Guo, Jianxin Sun, Jonathan Li, Caleb B Kallen, Ulhas P Naik, Ross Summer
Obesity is a significant risk factor for the acute respiratory distress syndrome (ARDS). The mechanisms underlying this association are unknown. We recently showed that diet-induced obese (DIO) mice exhibit pulmonary vascular endothelial dysfunction which is associated with enhanced susceptibility to lipopolysaccharide (LPS)-induced lung injury. Here, we demonstrate that lung endothelial dysfunction in DIO mice coincides with increased endoplasmic reticulum (ER) stress. Specifically, we observed enhanced expression of the major sensors of misfolded proteins including PERK, IREα and ATF6, in whole lung and in lung endothelial cells isolated from DIO mice...
March 9, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28248201/intravascular-hemolysis-and-the-pathophysiology-of-sickle-cell-disease
#7
REVIEW
Gregory J Kato, Martin H Steinberg, Mark T Gladwin
Hemolysis is a fundamental feature of sickle cell anemia that contributes to its pathophysiology and phenotypic variability. Decompartmentalized hemoglobin, arginase 1, asymmetric dimethylarginine, and adenine nucleotides are all products of hemolysis that promote vasomotor dysfunction, proliferative vasculopathy, and a multitude of clinical complications of pulmonary and systemic vasculopathy, including pulmonary hypertension, leg ulcers, priapism, chronic kidney disease, and large-artery ischemic stroke. Nitric oxide (NO) is inactivated by cell-free hemoglobin in a dioxygenation reaction that also oxidizes hemoglobin to methemoglobin, a non-oxygen-binding form of hemoglobin that readily loses heme...
March 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28242077/ex%C3%A2-vivo-lung-perfusion-model-to-study-pulmonary-tissue-extracellular-microvesicle-profiles
#8
Prashanth Vallabhajosyula, Laxminarayana Korutla, Andreas Habertheuer, Sanjana Reddy, Christian Schaufler, Jared Lasky, Joshua Diamond, Edward Cantu
BACKGROUND: Extracellular microvesicles (EVs) are being increasingly studied for their diagnostic potential. We investigated the feasibility of studying the kinetics and tissue-specific profiles of pulmonary EVs in the context of ex vivo lung perfusion (EVLP) used for salvaging marginal lungs for transplantation. METHODS: Perfusate from six marginal donor lungs placed on EVLP was collected at the following time points: 0, 10, and 60 minutes after and after perfusate exchange with Steen Solution; 120 and 180 minutes...
February 24, 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28236024/molecular-imaging-of-the-human-pulmonary-vascular-endothelium-in-pulmonary-hypertension-a-phase-ii-safety-and-proof-of-principle-trial
#9
François Harel, David Langleben, Steve Provencher, Alain Fournier, Vincent Finnerty, Quang T Nguyen, Myriam Letourneau, Xavier Levac, Gad Abikhzer, Jean Guimond, Asmaa Mansour, Marie-Claude Guertin, Jocelyn Dupuis
PURPOSE: The adrenomedullin receptor is densely expressed in the pulmonary vascular endothelium. PulmoBind, an adrenomedullin receptor ligand, was developed for molecular diagnosis of pulmonary vascular disease. We evaluated the safety of PulmoBind SPECT imaging and its capacity to detect pulmonary vascular disease associated with pulmonary hypertension (PH) in a human phase II study. METHODS: Thirty patients with pulmonary arterial hypertension (PAH, n = 23) or chronic thromboembolic PH (CTEPH, n = 7) in WHO functional class II (n = 26) or III (n = 4) were compared to 15 healthy controls...
February 24, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28203404/the-role-of-cyclooxygenase-2-in-the-protection-against-apoptosis-in-vascular-endothelial-cells-induced-by-cigarette-smoking
#10
Zhihui Shi, Yan Chen, Yanfang Pei, Yingjiao Long, Caihong Liu, Jun Cao, Ping Chen
BACKGROUND: Apoptosis has been demonstrated to be an important upstream event in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cyclooxygenase-2 (COX-2) seems to be biologically relevant in COPD. However, the role of COX-2 in the apoptosis in vascular endothelial cells induced by cigarette smoke extract (CSE) remains to be elucidated. Our recent study found that the prostacyclin, one of the COX products in the microvascular endothelium, inhibited apoptosis in the emphysematous lungs of rats induced by CSE...
January 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28190469/proanthocyanidins-from-vitis-vinifera-inhibit-oxidative-stress-induced-vascular-impairment-in-pulmonary-arteries-from-diabetic-rats
#11
Christian Pinna, Paolo Morazzoni, Angelo Sala
BACKGROUND: Vitis vinifera L. (grape seed extract) is a natural source of proanthocyanidins with antioxidant and free radical-scavenging activities. HYPOTHESIS: Grape seed extract supplementation may prevent vascular endothelium impairment associated with diabetes mellitus in rat pulmonary artery. STUDY DESIGN: We evaluated endothelial function of rat pulmonary artery ex-vivo at the intermediate stage (4 weeks) of streptozotocin (STZ)-induced diabetes mellitus...
February 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28137936/elabela-toddler-is-an-endogenous-agonist-of-the-apelin-apj-receptor-in-the-adult-cardiovascular-system-and-exogenous-administration-of-the-peptide-compensates-for-the-downregulation-of-its-expression-in-pulmonary-arterial-hypertension
#12
Peiran Yang, Cai Read, Rhoda E Kuc, Guido Buonincontri, Mark Southwood, Rubben Torella, Paul D Upton, Alexi Crosby, Stephen J Sawiak, T Adrian Carpenter, Robert C Glen, Nicholas W Morrell, Janet J Maguire, Anthony P Davenport
BACKGROUND: Elabela/toddler (ELA) is a critical cardiac developmental peptide that acts through the G-protein-coupled apelin receptor, despite lack of sequence similarity to the established ligand apelin. Our aim was to investigate the receptor pharmacology, expression pattern, and in vivo function of ELA peptides in the adult cardiovascular system, to seek evidence for alteration in pulmonary arterial hypertension (PAH) in which apelin signaling is downregulated, and to demonstrate attenuation of PAH severity with exogenous administration of ELA in a rat model...
March 21, 2017: Circulation
https://www.readbyqxmd.com/read/28130261/impact-of-thrombosis-on-pulmonary-endothelial-injury-and-repair-following-sepsis
#13
Colin Evans, You-Yang Zhao
The prevailing morbidity and mortality in sepsis are largely due to multiple organ dysfunction (MOD), most commonly lung injury, as well as renal and cardiac dysfunction. Despite recent advances in defining many aspects of the pathogenesis of sepsis-related MOD, including acute respiratory distress syndrome (ARDS), there are currently no effective pharmacological or cell-based treatments for the disease. Human and animal studies have shown that pulmonary thrombosis is common in sepsis-induced ARDS, and pre-clinical studies have shown that anti-coagulation may improve outcome following sepsis challenge...
January 27, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28110121/s100a12-friend-or-foe-in-pulmonary-tuberculosis
#14
Vahid Bagheri
In humans, S100A12 (also named Calgranulin C and EN-RAGE) is mainly expressed and secreted by neutrophil granulocytes. Extracellular S100A12 is involved in innate immune responses against microorganisms and parasites. S100A12 is a ligand for the receptor for advanced glycation end products (RAGE), which is a cell surface receptor on macrophages, endothelium, and lymphocytes. In a recent study, Realegeno et al. showed that S100A12 exerts antimicrobial activity against Mycobacterium leprae in infected human macrophages...
April 2017: Cytokine
https://www.readbyqxmd.com/read/28107214/loss-of-syndecan-1-abrogates-the-pulmonary-protective-phenotype-induced-by-plasma-after-hemorrhagic-shock
#15
Feng Wu, Zhanglong Peng, Pyong Woo Park, Rosemary A Kozar
Syndecan-1 is considered a biomarker of injury to the endothelial glycocalyx following hemorrhagic shock, with shedding of sdc1 deleterious. Resuscitation with fresh frozen plasma (FFP) has been correlated with restitution of pulmonary sdc1 and reduction of lung injury, but the precise contribution of sdc1 to FFPs protection in the lung remains unclear. Human lung endothelial cells were used to assess the time and dose dependent effect of FFP on sdc1 expression and the effect of sdc1 silencing on in vitro endothelial cell permeability and actin stress fiber formation...
January 19, 2017: Shock
https://www.readbyqxmd.com/read/28104688/mice-with-a-deficiency-in-clec-2-are-protected-against-deep-vein-thrombosis
#16
Holly Payne, Tatyana Ponomaryov, Steve P Watson, Alexander Brill
Deep vein thrombosis (DVT) with its major complication, pulmonary embolism, is a global health problem. Mechanisms of DVT remain incompletely understood. Platelets play a role in DVT but the impact of specific platelet receptors remains unclear. Platelet C-type lectin-like receptor 2 (CLEC-2) is known to maintain the physiological state of blood vasculature under inflammatory conditions. DVT is a thromboinflammatory disorder developing largely as sterile inflammation in the vessel wall. We hypothesized therefore that CLEC-2 might play a role in DVT...
January 19, 2017: Blood
https://www.readbyqxmd.com/read/28100233/the-role-of-the-endothelium-in-asthma-and-chronic-obstructive-pulmonary-disease-copd
#17
REVIEW
Clara E Green, Alice M Turner
COPD and asthma are important chronic inflammatory disorders with a high associated morbidity. Much research has concentrated on the role of inflammatory cells, such as the neutrophil, in these diseases, but relatively little focus has been given to the endothelial tissue, through which inflammatory cells must transmigrate to reach the lung parenchyma and cause damage. There is evidence that there is an abnormal amount of endothelial tissue in COPD and asthma and that this tissue and its' progenitor cells behave in a dysfunctional manner...
January 18, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28087752/deficient-retinoid-driven-angiogenesis-may-contribute-to-failure-of-adult-human-lung-regeneration-in-emphysema
#18
John-Poul Ng-Blichfeldt, Joana Alçada, M Angeles Montero, Charlotte H Dean, Uta Griesenbach, Mark J Griffiths, Matthew Hind
BACKGROUND: Molecular pathways that regulate alveolar development and adult repair represent potential therapeutic targets for emphysema. Signalling via retinoic acid (RA), derived from vitamin A, is required for mammalian alveologenesis, and exogenous RA can induce alveolar regeneration in rodents. Little is known about RA signalling in the human lung and its potential role in lung disease. OBJECTIVES: To examine regulation of human alveolar epithelial and endothelial repair by RA, and characterise RA signalling in human emphysema...
January 13, 2017: Thorax
https://www.readbyqxmd.com/read/28079595/acetylated-cyclophilin-a-is-a-major-mediator-in-hypoxia-induced-autophagy-and-pulmonary-vascular-angiogenesis
#19
Min Mao, Xiufeng Yu, Xin Ge, Rui Gu, Qian Li, Shasha Song, Xiaodong Zheng, Tingting Shen, Xuecang Li, Yao Fu, Jiali Li, Daling Zhu
BACKGROUND: Autophagy is a major intracellular degradation and recycling process that maintains cellular homeostasis, which is involved in structural and functional abnormalities of pulmonary vasculature in hypoxic pulmonary arterial hypertension (HPAH). Cyclophilin A (CyPA) is a secreted, oxidative stress-induced factor. Its role in inducing autophagy and augmenting endothelial cell dysfunction has never been explored. METHODS: Lungs from rats exposed to chronic hypoxia were examined for autophagy with electron microscopy, western blotting, and fluorescence microscopy...
April 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28068653/exosomes-derived-from-human-pulmonary-artery-endothelial-cells-shift-the-balance-between-proliferation-and-apoptosis-of-smooth-muscle-cells
#20
Lin Zhao, Hui Luo, Xiaohui Li, Tangzhiming Li, Jingni He, Qiangqiang Qi, Yuwei Liu, Zaixin Yu
BACKGROUND: The overproliferation of pulmonary vascular cells is noted in pulmonary hypertension. The role of exosomes from pulmonary artery endothelial cells (PAEC) in the proliferation and apoptosis of pulmonary artery smooth muscle cells (PASMC) remains unclear. METHODS: Exosomes were isolated and purified from the culture medium of PAEC using a commercial kit. Lipopolysaccharide (LPS), hypoxia, and hydrogen peroxide were utilized to induce PAEC injury. Coculture of PAEC and PASMC was conducted using Transwell plates, and GW4869 was applied to inhibit exosome release...
January 10, 2017: Cardiology
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