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Pulmonary endothelium

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https://www.readbyqxmd.com/read/29449428/a-novel-piperidine-identified-by-stem-cell-based-screening-attenuates-pulmonary-arterial-hypertension-via-regulating-bmp2-and-ptgs2-levels
#1
Yanjiang Xing, Shuang Zhao, Qingxia Wei, Shiqiang Gong, Xin Zhao, Fang Zhou, Rafia Ai-Lamki, Daniel Ortmann, Mingxia Du, Roger Pedersen, Guangdong Shang, Shuyi Si, Nicholas W Morrell, Jun Yang
Genetic defects in bone morphogenetic protein type-II receptor (BMPRII) signalling and inflammation contribute to the pathogenesis of pulmonary arterial hypertension (PAH). The receptor is activated by BMP ligands, which also enhance BMPR2 transcription. A small molecule BMP upregulator with selectivity on vascular endothelium would represent a desirable therapeutic intervention for PAH.We assayed compounds identified in the screening of BMP2 upregulators for their ability to increase expression of Inhibitor of DNA binding 1 (Id1), using a dual reporter driven specifically in human embryonic stem cell (hESC)-derived endothelial cells (ECs)...
February 15, 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29435736/cardiovascular-studies-in-patients-with-chronic-obstructive-pulmonary-disease-due-to-biomass-smoke-or-tobacco
#2
Rafael Golpe, Pilar Sanjuán-López, Irene Martín-Robles, Carlos González-Juanatey, Luis Pérez-de-Llano, José L López-Campos
BACKGROUND AND OBJECTIVE: The cardiovascular effects of biomass smoke exposure in patients with chronic obstructive pulmonary disease are not well characterized, and few studies have assessed the possible differences between patients with disease caused by biomass smoke and tobacco. The aim of this study was to search for differences in cardiovascular variables between both types of the disease. METHODS: Twenty subjects (15 men, 5 women) with chronic obstructive pulmonary disease caused by tobacco were matched one to one for sex, age, and forced expiratory volume in 1 s to 20 patients with biomass-related disease...
February 12, 2018: Lung
https://www.readbyqxmd.com/read/29413495/effects-of-respiratory-muscle-training-on-endothelium-and-oxidative-stress-biomarkers-in-hemodialysis-patients-a-randomized-clinical-trial
#3
Nataly Gurgel Campos, Débora Fortes Marizeiro, Ana Carolina Lins Florêncio, Ítalo Caldas Silva, Gdayllon Cavalcante Meneses, Gabriela Freire Bezerra, Alice Maria Costa Martins, Alexandre Braga Libório
INTRODUCTION: Hemodialysis (HD) patients have altered pulmonary function and this is associated with impaired endothelial function and cardiovascular events. Respiratory muscle training (RMT) has the potential to improve cardiovascular outcomes in patients undergoing maintenance HD. Here, we evaluated the effects of RMT on endothelium/glycocalyx, oxidative stress biomarkers and pulmonary function test in HD patients. METHODS: This is a randomized controlled clinical trial including 41 patients undergoing thrice-weekly maintenance HD...
January 2018: Respiratory Medicine
https://www.readbyqxmd.com/read/29408197/long-noncoding-rna-lispr1-is-required-for-s1p-signaling-and-endothelial-cell-function
#4
Ivana Josipovic, Beatrice Pflüger, Christian Fork, Andrea E Vasconez, James A Oo, Juliane Hitzel, Sandra Seredinski, Elisabetta Gamen, Dagmar Meyer Zu Heringdorf, Wei Chen, Mario Looso, Soni Savai Pullamsetti, Ralf P Brandes, Matthias S Leisegang
Sphingosine-1-Phosphate (S1P) is a potent signaling lipid. The effects of S1P are mediated by the five S1P receptors (S1PR). In the endothelium S1PR1 is the predominant receptor and thus S1PR1 abundance limits S1P signaling. Recently, lncRNAs were identified as a novel class of molecules regulating gene expression. Interestingly, the lncRNA NONHSAT004848 (LISPR1, Long intergenic noncoding RNA antisense to S1PR1), is closely positioned to the S1P1 receptors gene and in part shares its promoter region. We hypothesize that LISPR1 controls endothelial S1PR1 expression and thus S1P-induced signaling in endothelial cells...
January 31, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29402133/immunomodulatory-effect-of-hemozoin-on-pneumocyte-apoptosis-via-card9-pathway-a-possibly-retarding-pulmonary-resolution
#5
Sitang Maknitikul, Natthanej Luplertlop, Urai Chaisri, Yaowapa Maneerat, Sumate Ampawong
Plasmodium falciparum, the most virulent malaria parasite species, causes severe symptoms especially acute lung injury (ALI), of which characterized by alveolar epithelium and endothelium destruction and accelerated to blood-gas-barrier breakdown. Parasitized erythrocytes, endothelial cells, monocytes, and cytokines are all involved in this mechanism, but hemozoin (HZ), the parasitic waste from heme detoxification, also mainly contributes. In addition, it is not clear why type II pneumocyte proliferation, alveolar restorative stage, is rare in malaria-associated ALI...
January 1, 2018: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29394283/lyophilized-plasma-attenuates-vascular-permeability-inflammation-and-lung-injury-in-hemorrhagic-shock
#6
Shibani Pati, Zhanglong Peng, Katherine Wataha, Byron Miyazawa, Daniel R Potter, Rosemary A Kozar
In severe trauma and hemorrhage the early and empiric use of fresh frozen plasma (FFP) is associated with decreased morbidity and mortality. However, utilization of FFP comes with the significant burden of shipping and storage of frozen blood products. Dried or lyophilized plasma (LP) can be stored at room temperature, transported easily, reconstituted rapidly with ready availability in remote and austere environments. We have previously demonstrated that FFP mitigates the endothelial injury that ensues after hemorrhagic shock (HS)...
2018: PloS One
https://www.readbyqxmd.com/read/29387414/role-of-p-selectin-in-thromboembolic-events-in-patients-with-cancer
#7
Lúcio Flávio Barbour Fernandes, José Humberto T G Fregnani, Célia Maria Cássaro Strunz, Adriana de Andrade Ramos Nogueira, Adhemar Longatto-Filho
The objective of the present study was to evaluate the role of P-selectin in patients with cancer with suspected thromboembolic events (TEEs). Patients with cancer have a four times greater risk of developing TEEs. P-selectin is a glycoprotein that has the function of facilitating the interaction (adhesion) of leukocytes with the endothelium, or with platelets. There is a well-defined relationship between P-selectin and thrombosis; however, it is likely that the cut-off value of P-selectin for patients with cancer should be considered differently from that of the general population...
January 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29373038/actin-polymerization-contributes-to-enhanced-pulmonary-vasoconstrictor-reactivity-following-chronic-hypoxia
#8
Laura Weise-Cross, Michelle Sands, Joshua R Sheak, Brad R S Broughton, Jessica B Snow, Laura V Gonzalez Bosc, Nikki L Jernigan, Benjimen R Walker, Thomas C Resta
Chronic hypoxia (CH) augments basal and endothelin 1 (ET-1)-induced pulmonary vasoconstrictor reactivity through reactive oxygen species (ROS) generation and RhoA/Rho kinase (ROCK)-dependent myofilament Ca2+ sensitization. Because ROCK promotes actin polymerization and the actin cytoskeleton regulates smooth muscle tension, we hypothesized that actin polymerization is required for enhanced basal and ET-1-dependent vasoconstriction following CH. To test this hypothesis, both endpoints were monitored in pressurized, endothelium-disrupted pulmonary arteries (4th-5th order) from control and CH (4 wk at 0...
January 26, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29363851/wild-type-p53-enhances-endothelial-barrier-function-by-mediating-rac1-signalling-and-rhoa-inhibition
#9
Nektarios Barabutis, Christiana Dimitropoulou, Betsy Gregory, John D Catravas
Inflammation is the major cause of endothelial barrier hyper-permeability, associated with acute lung injury and acute respiratory distress syndrome. This study reports that p53 "orchestrates" the defence of vascular endothelium against LPS, by mediating the opposing actions of Rac1 and RhoA in pulmonary tissues. Human lung microvascular endothelial cells treated with HSP90 inhibitors activated both Rac1- and P21-activated kinase, which is an essential element of vascular barrier function. 17AAG increased the phosphorylation of both LIMK and cofilin, in contrast to LPS which counteracted those effects...
January 24, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29363240/magnesium-attenuates-endothelin-1-induced-vasoreactivity-and-enhances-vasodilation-in-mouse-pulmonary-arteries-modulation-by-chronic-hypoxic-pulmonary-hypertension
#10
Yun-Ping Mu, Qiu-Hong Huang, Jie-Ling Zhu, Si-Yi Zheng, Fu-Rong Yan, Xiao-Ling Zhuang, James S K Sham, Mo-Jun Lin
Pulmonary hypertension (PH) is characterized by enhanced vasoreactivity and sustained pulmonary vasoconstriction, arising from the aberrant Ca2+ homeostasis in pulmonary arterial smooth muscle cells. In addition to Ca2+ , magnesium, the most abundant intracellular divalent cation, also plays critical roles in many cellular processes that regulate cardiovascular functions. Recent findings suggested that magnesium regulates vascular functions by altering the vascular responses to vasodilator and vasoactive agonists, and affects endothelial function by modulating endothelium-dependent vasodilation in hypertension...
January 23, 2018: Experimental Physiology
https://www.readbyqxmd.com/read/29362409/cancer-cell-derived-von-willebrand-factor-enhanced-metastasis-of-gastric-adenocarcinoma
#11
Ai-Jun Yang, Min Wang, Yan Wang, Wei Cai, Qiang Li, Ting-Ting Zhao, Li-Han Zhang, Katie Houck, Xu Chen, Yan-Ling Jin, Ji-Ying Mu, Jing-Fei Dong, Min Li
Cancer prognosis is poor for patients with blood-borne metastasis. Platelets are known to assist cancer cells in transmigrating through the endothelium, but ligands for the platelet-mediated cancer metastasis remain poorly defined. von Willebrand factor (vWF) is a major platelet ligand that has been widely used as a biomarker in cancer and associated inflammation. However, its functional role in cancer growth and metastasis is largely unknown. Here we report that gastric cancer cells from patients and cells from two well-established gastric cancer lines express vWF and secrete it into the circulation, upon which it rapidly becomes cell-bound to mediate cancer-cell aggregation and interaction with platelets and endothelial cells...
January 24, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29361046/targeted-endothelial-gene-deletion-of-triggering-receptor-expressed-on-myeloid-cells-1-protects-mice-during-septic-shock
#12
Lucie Jolly, Kevin Carrasco, Marc Derive, Jérémie Lemarié, Amir Boufenzer, Sébastien Gibot
AIMS: TREM-1 (Triggering Receptor Expressed on Myeloid cells-1) is an immunoreceptor expressed on neutrophils and monocytes/macrophages whose role is to amplify the inflammatory response driven by Toll-Like Receptors engagement. The pharmacological inhibition of TREM-1 confers protection in several pre-clinical models of acute inflammation. In this study, we aimed to decipher the role of TREM-1 on the endothelium. METHODS AND RESULTS: We first showed by qRT-PCR, flow cytometry and confocal microscopy that TREM-1 was expressed in human pulmonary microvascular endothelial cells as well as in mouse vasculature (aorta, mesenteric artery, and pulmonary vessels)...
January 19, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29351457/important-role-of-endothelium-dependent-hyperpolarization-in-pulmonary-microcirculation-in-male-mice-implications-for-hypoxia-induced-pulmonary-hypertension
#13
Shuhei Tanaka, Takashi Shiroto, Shigeo Godo, Hiroki Saito, Yosuke Ikumi, Akiyo Ito, Shoko Kajitani, Saori Sato, Hiroaki Shimokawa
Endothelium-dependent hyperpolarization (EDH) plays important roles in systemic circulation, whereas its role in pulmonary circulation remains largely unknown. Furthermore, the underlying mechanisms of pulmonary hypertension (PH) also remain to be elucidated. We thus aimed to elucidate the role of EDH in pulmonary circulation in general and in PH in particular. In isolated perfused lung using male wild-type mice, endothelium-dependent relaxations to bradykinin (BK) were significantly reduced in the presence of Nω-nitro-L-arginine (L-NNA) by ~50% as compared with those in the presence of indomethacin, and the combination of apamin plus charybdotoxin abolished the residual relaxations, showing the comparable contributions of nitric oxide (NO) and EDH in pulmonary microcirculation under physiological conditions...
January 5, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29343759/incorporation-of-iloprost-in-phospholipase-resistant-phospholipid-scaffold-enhances-its-barrier-protective-effects-on-pulmonary-endothelium
#14
Olga Oskolkova, Nicolene Sarich, Yufeng Tian, Grzegorz Gawlak, Fanyong Meng, Valery N Bochkov, Evgeny Berdyshev, Anna A Birukova, Konstantin G Birukov
Correction of barrier dysfunction and inflammation in acute lung injury (ALI) represents an important problem. Previous studies demonstrate barrier-protective and anti-inflammatory effects of bioactive lipid prostacyclin and its stable analog iloprost (ILO). We generated a phospholipase resistant synthetic phospholipid with iloprost attached at the sn-2 position (ILO-PC) and investigated its biological effects. In comparison to free ILO, ILO-PC caused sustained endothelial cell (EC) barrier enhancement, linked to more prolonged activation of Rap1 and Rac1 GTPases and their cytoskeletal and cell junction effectors: cortactin, PAK1, p120-catenin and VE-cadherin...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29295855/the-%C3%AE-2-agonist-terbutaline-specifically-decreases-pulmonary-arterial-pressure-under-normoxia-and-hypoxia-via-%C3%AE-adrenoceptor-antagonism
#15
Vanessa Neumann, Ralf Knies, Alexander Seidinger, Annika Simon, Kristina Lorenz, Michaela Matthey, Johannes Breuer, Daniela Wenzel
Pulmonary hypertension is a severe, incurable disease with a poor prognosis. Although treatment regimens have improved during the last 2 decades, current pharmacologic strategies are limited and focus on the modulation of only a few pathways related to endothelin, NO, and prostacyclin signaling. Therefore, the identification of novel molecular targets is urgently needed. We found that the β2 adrenoceptor (AR) agonists terbutaline (TER) and salbutamol induced a dose-dependent vasorelaxation in large pulmonary arteries but not aortas of mouse...
January 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29290576/leukotriene-b4-mediated-neutrophil-recruitment-causes-pulmonary-capillaritis-during-lethal-fungal-sepsis
#16
Esther K S Lee, Mark R Gillrie, Lu Li, Jason W Arnason, Jung Hwan Kim, Liane Babes, Yuefei Lou, Amir Sanati-Nezhad, Stephen K Kyei, Margaret M Kelly, Christopher H Mody, May Ho, Bryan G Yipp
Candida albicans bloodstream infection causes fungal septicaemia and death in over half of afflicted patients. Polymorphonuclear leukocytes (PMN) mediate defense against invasive candidiasis, but their role in protection versus tissue injury and sepsis is unclear. We observe PMN intravascular swarming and subsequent clustering in response to C. albicans yeast in a lethal septic mouse and human pulmonary circulation model. Live C. albicans sequester to the endothelium and are immediately captured by complement-dependent PMN chemotaxis, which is required for host survival...
December 28, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/29288384/comparative-view-of-lung-vascular-endothelium-of-cattle-horses-and-water-buffalo
#17
David Schneberger, Ram S Sethi, Baljit Singh
Endothelium plays an important role in maintaining the vascular barrier and physiological homeostasis. Endothelium also is fundamental to the initiation and regulation of inflammation. Endothelium demonstrates phenotypic and functional heterogeneity not only among various organs but also within an organ. One of the striking examples would be the pulmonary endothelium that participates in creating blood-air barrier. Endothelium in large pulmonary blood vessels is distinct in structure and function from that lining of the pulmonary capillaries...
2018: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/29275372/nitric-oxide-dependent-feedback-loop-regulates-transient-receptor-potential-vanilloid-4-trpv4-channel-cooperativity-and-endothelial-function-in-small-pulmonary-arteries
#18
Corina Marziano, Kwangseok Hong, Eric L Cope, Michael I Kotlikoff, Brant E Isakson, Swapnil K Sonkusare
BACKGROUND: Recent studies demonstrate that spatially restricted, local Ca2+ signals are key regulators of endothelium-dependent vasodilation in systemic circulation. There are drastic functional differences between pulmonary arteries (PAs) and systemic arteries, but the local Ca2+ signals that control endothelium-dependent vasodilation of PAs are not known. Localized, unitary Ca2+ influx events through transient receptor potential vanilloid 4 (TRPV4) channels, termed TRPV4 sparklets, regulate endothelium-dependent vasodilation in resistance-sized mesenteric arteries via activation of Ca2+-dependent K+ channels...
December 23, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29245182/an-efficient-parallel-simulation-of-unsteady-blood-flows-in-patient-specific-pulmonary-artery
#19
Fande Kong, Vitaly Kheyfets, Ender Finol, Xiao-Chuan Cai
Simulation of blood flows in the pulmonary artery provides some insight into certain diseases by examining the relationship between some continuum metrics, e.g. the wall shear stress acting on the vascular endothelium, which responds to flow-induced mechanical forces by releasing vasodilators/constrictors. In [?kheyfets2015patient], V. Kheyfets studies numerically a patient-specific pulmonary circulation to show that decreasing wall shear stress is correlated with increasing pulmonary vascular impedance. In this paper, we develop a scalable parallel algorithm based on domain decomposition methods to investigate an unsteady model with patient specific pulsatile waveforms as the inlet boundary condition...
December 15, 2017: International Journal for Numerical Methods in Biomedical Engineering
https://www.readbyqxmd.com/read/29226623/distortion-of-kb-estimates-of-endothelin-1-eta-and-etb-receptor-antagonists-in-pulmonary-arteries-possible-role-of-an-endothelin-1-clearance-mechanism
#20
James A Angus, Richard J A Hughes, Christine E Wright
Dual endothelin ETA and ETB receptor antagonists are approved therapy for pulmonary artery hypertension (PAH). We hypothesized that ETB receptor-mediated clearance of endothelin-1 at specific vascular sites may compromise this targeted therapy. Concentration-response curves (CRC) to endothelin-1 or the ETB agonist sarafotoxin S6c were constructed, with endothelin receptor antagonists, in various rat and mouse isolated arteries using wire myography or in rat isolated trachea. In rat small mesenteric arteries, bosentan displaced endothelin-1 CRC competitively indicative of ETA receptor antagonism...
December 2017: Pharmacology Research & Perspectives
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