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Pulmonary endothelium

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https://www.readbyqxmd.com/read/28629122/age-related-changes-in-immunological-and-physiological-responses-following-pulmonary-challenge
#1
REVIEW
Edmund J Miller, Helena M Linge
This review examines the current status of knowledge of sepsis and pneumonia in the elderly population and how the dynamics of the pulmonary challenge affects outcome and consequences. Led by an unprecedented shift in demographics, where a larger proportion of the population will reach an older age, clinical and experimental research shows that aging is associated with certain pulmonary changes, but it is during infectious insult of the lungs, as in the case of pneumonia, that the age-related differences in responsiveness and endurance become obvious and lead to a worse outcome than in the younger population...
June 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28628347/preventive-treatment-with-atorvastatin-ameliorates-endothelial-dysfunction-of-small-pulmonary-arteries-in-monocrotaline-induced-pulmonary-hypertensive-rats
#2
Zhihong Lin, Zhi Jiang, Xiaodong Huang, Xiaoqi Cai, Huajun Wang, Liangdi Xie
This study examined the effects of preventive atorvastatin (Ator) treatment on vasodilatation of small pulmonary arteries (SPAs) in monocrotaline (MCT)-induced pulmonary hypertensive rats. SD rats were randomly assigned to: normal control (Ctr), pulmonary arterial hypertension (PAH), PAH treated with 5 mg/kg/d Ator (LAtor), or 10 mg/kg/d Ator (HAtor). PAH was induced by MCT injection (40 mg/kg, i.p.). Mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index (RVHI%), endothelium-dependent relaxations (EDdRs), and endothelium-independent relaxations (EDiRs) were determined...
June 19, 2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28627093/characterization-of-thrombosis-in-patients-with-proteus-syndrome
#3
Kim M Keppler-Noreuil, Jay N Lozier, Julie C Sapp, Leslie G Biesecker
Patients with overgrowth and complex vascular malformation syndromes, including Proteus syndrome have an increased risk of thromboembolism. Proteus syndrome is a mosaic, progressive overgrowth disorder involving vasculature, skin, and skeleton, and caused by a somatic activating mutation in AKT1. We conducted a comprehensive review of the medical histories and hematologic evaluations of 57 patients with Proteus syndrome to identify potential risk factors for thrombosis. We found that six of ten patients, who were deceased, died secondary to deep venous thrombosis and/or pulmonary embolism...
June 19, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28626833/the-lung-is-a-host-defense-niche-for-immediate-neutrophil-mediated-vascular-protection
#4
Bryan G Yipp, Jung Hwan Kim, Ronald Lima, Lori D Zbytnuik, Björn Petri, Nick Swanlund, May Ho, Vivian G Szeto, Tamar Tak, Leo Koenderman, Peter Pickkers, Anton T J Tool, Taco W Kuijpers, Timo K van den Berg, Mark R Looney, Matthew F Krummel, Paul Kubes
Bloodstream infection is a hallmark of sepsis, a medically emergent condition requiring rapid treatment. However, upregulation of host defense proteins through toll-like receptors and NFκB requires hours after endotoxin detection. Using confocal pulmonary intravital microscopy, we identified that the lung provides a TLR4-Myd88-and abl tyrosine kinase-dependent niche for immediate CD11b-dependent neutrophil responses to endotoxin and Gram-negative bloodstream pathogens. In an in vivo model of bacteremia, neutrophils crawled to and rapidly phagocytosed Escherichia coli sequestered to the lung endothelium...
April 28, 2017: Science Immunology
https://www.readbyqxmd.com/read/28611413/a-microengineered-model-of-rbc-transfusion-induced-pulmonary-vascular-injury
#5
Jeongyun Seo, David Conegliano, Megan Farrell, Minseon Cho, Xueting Ding, Thomas Seykora, Danielle Qing, Nilam S Mangalmurti, Dongeun Huh
Red blood cell (RBC) transfusion poses significant risks to critically ill patients by increasing their susceptibility to acute respiratory distress syndrome. While the underlying mechanisms of this life-threatening syndrome remain elusive, studies suggest that RBC-induced microvascular injury in the distal lung plays a central role in the development of lung injury following blood transfusion. Here we present a novel microengineering strategy to model and investigate this key disease process. Specifically, we created a microdevice for culturing primary human lung endothelial cells under physiological flow conditions to recapitulate the morphology and hemodynamic environment of the pulmonary microvascular endothelium in vivo...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28602360/the-role-of-platelets-in-autoimmunity-vasculopathy-and-fibrosis-implications-for-systemic-sclerosis
#6
REVIEW
Konstantinos Ntelis, Elena E Solomou, Lazaros Sakkas, Stamatis-Nick Liossis, Dimitrios Daoussis
INTRODUCTION: Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, autoimmunity, and widespread dermal and visceral fibrosis. This article summarizes the current knowledge about the potential contribution of platelets in the disease process and the rationale of targeting platelets as an adjunct treatment for SSc. METHODS: We performed an electronic search (Medline) using the keywords platelets, systemic sclerosis, autoimmunity, fibrosis, Raynaud, and pulmonary arterial hypertension...
May 23, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/28596957/heterogeneous-vascular-bed-responses-to-pulmonary-titanium-dioxide-nanoparticle-exposure
#7
Alaeddin B Abukabda, Phoebe A Stapleton, Carroll R McBride, Jinghai Yi, Timothy R Nurkiewicz
A growing body of research links engineered nanomaterial (ENM) exposure to adverse cardiovascular endpoints. The purpose of this study was to evaluate the impact of ENM exposure on vascular reactivity in discrete segments so that we may determine the most sensitive levels of the vasculature where these negative cardiovascular effects are manifest. We hypothesized that acute nano-TiO2 exposure differentially affects reactivity with a more robust impairment in the microcirculation. Sprague-Dawley rats (8-10 weeks) were exposed to nano-TiO2via intratracheal instillation (20, 100, or 200 µg suspended per 250 µL of vehicle) 24 h prior to vascular assessments...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28596374/lrp1-dependent-bmper-signaling-regulates-lipopolysaccharide-induced-vascular-inflammation
#8
Pamela Lockyer, Hua Mao, Qiying Fan, Luge Li, Li-Yuan Yu-Lee, N Tony Eissa, Cam Patterson, Liang Xie, Xinchun Pi
OBJECTIVE: Bacterial endotoxin (lipopolysaccharide)-mediated sepsis involves dysregulated systemic inflammation, which injures the lung and other organs, often fatally. Vascular endothelial cells act as both targets and mediators of lipopolysaccharide-induced inflammatory responses. Dysfunction of endothelium results in increases of proinflammatory cytokine production and permeability leakage. BMPER (bone morphogenetic protein-binding endothelial regulator), an extracellular modulator of bone morphogenetic protein signaling, has been identified as a vital component in chronic endothelial inflammatory responses and atherosclerosis...
June 8, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28552597/vasodilation-effect-of-volatile-oil-from-allium-macrostemon-bunge-are-mediated-by-pka-no-pathway-and-its-constituent-dimethyl-disulfide-in-isolated-rat-pulmonary-arterials
#9
Chenghua Han, Jing Qi, Sainan Gao, Chunxiang Li, Ying Ma, Jing Wang, Yuhua Bai, Xiaodong Zheng
The present study aimed to investigate the vasodilation effects of Allium macrostemon Bunge (AMB) on isolated rat pulmonary arterials (PAs) and to assess the underling mechanisms. The volatile oil was extracted by steam distillation from the bulbs of AMB. Then the volatile oil from AMB was studied on isolated rat PA, removal of endothelium, or pretreatment with nitro oxide (NO) synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME), or with protein kinase A (PKA) inhibitor PKI but not cyclooxygenase inhibitor indomethacin significantly blocked the AMB induced relaxation on PE-contracted PA rings...
May 26, 2017: Fitoterapia
https://www.readbyqxmd.com/read/28542132/inhibition-of-sdf-1-receptors-cxcr4-and-cxcr7-attenuates-acute-pulmonary-inflammation-via-the-adenosine-a2b-receptor-on-blood-cells
#10
Franziska Magdalena Konrad, Nadine Meichssner, Annette Bury, Kristian-Christos Ngamsri, Jörg Reutershan
Acute pulmonary inflammation is characterized by migration of polymorphonuclear neutrophils into the different compartments of the lung. Recent studies showed evidence that the chemokine stromal cell-derived factor (SDF)-1 and its receptors CXCR4 and CXCR7 influence migration of immune cells and their activity was linked to adenosine concentrations. We investigated the particular role of CXCR4- and CXCR7-inhibition and the potential link to the adenosine A2B-receptor, which plays an important anti-inflammatory role in the lung...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28535764/in-smokers-sonic-hedgehog-modulates-pulmonary-endothelial-function-through-vascular-endothelial-growth-factor
#11
Priscilla Henno, Stanislas Grassin-Delyle, Emeline Belle, Marion Brollo, Emmanuel Naline, Edouard Sage, Philippe Devillier, Dominique Israël-Biet
BACKGROUND: Tobacco-induced pulmonary vascular disease is partly driven by endothelial dysfunction. The Sonic hedgehog (SHH) pathway is involved in vascular physiology. We sought to establish whether the SHH pathway has a role in pulmonary endothelial dysfunction in smokers. METHODS: The ex vivo endothelium-dependent relaxation of pulmonary artery rings in response to acetylcholine (Ach) was compared in 34 current or ex-smokers and 8 never-smokers. The results were expressed as a percentage of the contraction with phenylephrine...
May 23, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28523109/discovery-of-gsk2193874-an-orally-active-potent-and-selective-blocker-of-transient-receptor-potential-vanilloid-4
#12
Mui Cheung, Weike Bao, David J Behm, Carl A Brooks, Michael J Bury, Sarah E Dowdell, Hilary S Eidam, Ryan M Fox, Krista B Goodman, Dennis A Holt, Dennis Lee, Theresa J Roethke, Robert N Willette, Xiaoping Xu, Guosen Ye, Kevin S Thorneloe
Transient Receptor Potential Vanilloid 4 (TRPV4) is a member of the Transient Receptor Potential (TRP) superfamily of cation channels. TRPV4 is expressed in the vascular endothelium in the lung and regulates the integrity of the alveolar septal barrier. Increased pulmonary vascular pressure evokes TRPV4-dependent pulmonary edema, and therefore, inhibition of TRPV4 represents a novel approach for the treatment of pulmonary edema associated with conditions such as congestive heart failure. Herein we report the discovery of an orally active, potent, and selective TRPV4 blocker, 3-(1,4'-bipiperidin-1'-ylmethyl)-7-bromo-N-(1-phenylcyclopropyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxamide (GSK2193874, 28) after addressing an unexpected off-target cardiovascular liability observed from in vivo studies...
May 11, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28522681/endothelial-nox1-oxidase-assembly-in-human-pulmonary-arterial-hypertension-driver-of-gremlin1-mediated-proliferation
#13
Imad Al Ghouleh, Sanghamitra Sahoo, Daniel N Meijles, Jefferson H Amaral, Daniel S de Jesus, John Sembrat, Mauricio Rojas, Dmitry A Goncharov, Elena A Goncharova, Patrick J Pagano
Background: Pulmonary arterial hypertension (PAH) is a rapidly degenerating and devastating disease of increased pulmonary vessel resistance leading to right heart failure. Palliative modalities remain limited despite recent endeavors to investigate the mechanisms underlying increased pulmonary vascular resistance, i.e. aberrant vascular remodeling and occlusion. However, little is known of the molecular mechanisms responsible for endothelial proliferation, a root cause of PAH-associated vascular remodeling...
May 18, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28522438/anti-inflammatory-effects-of-oxpapc-involve-endothelial-cell-mediated-generation-of-lxa4
#14
Yunbo Ke, Noureddine Zebda, Olga Oskokova, Taras Afonyushkin, Evgeny Berdyshev, Yufeng Tian, Fanyong Meng, Nicolene Sarich, Valery N Bochkov, Ji Ming Wang, Anna A Birukova, Konstantin G Birukov
Rationale: Oxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine generates a group of bioactive oxidized phospholipid products (OxPAPC) with a broad range of biological activities. Barrier-enhancing and anti-inflammatory effects of OxPAPC on pulmonary endothelial cells (EC) are critical for prevention of acute lung injury caused by bacterial pathogens or excessive mechanical ventilation. Anti-inflammatory properties of OxPAPC are associated with its antagonistic effects on toll-like receptors and suppression of RhoA GTPase signaling...
May 18, 2017: Circulation Research
https://www.readbyqxmd.com/read/28516446/a-primary-human-lung-alveolus-on-a-chip-model-of-intravascular-thrombosis-for-assessment-of-therapeutics
#15
Abhishek Jain, Riccardo Barrile, Andries D van der Meer, Akiko Mammoto, Tadanori Mammoto, Karen De Ceunynck, Omozuanvbo Aisiku, Monicah A Otieno, Calvert S Louden, Geraldine A Hamilton, Robert Flaumenhaft, Donald E Ingber
Pulmonary thrombosis is a significant cause of patient mortality, however, there are no effective in vitro models of thrombi formation in human lung microvessels, that could also assess therapeutics and toxicology of antithrombotic drugs. Here we show that a microfluidic lung alveolus-on-a-chip lined by human primary alveolar epithelium interfaced with endothelium, and cultured under flowing whole blood can be used to perform quantitative analysis of organ-level contributions to inflammation-induced thrombosis...
May 17, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28497392/xuebijing-injection-increases-early-survival-rate-by-alleviating-pulmonary-vasopermeability-in-rats-subjected-to-severe-burns
#16
Yue-Long Dai, Jing-Yuan Li, Hui-Ying Bai, Si Liu, Yong-Qi Dou, Sen Hu
OBJECTIVES: To investigate the effects of Xuebijing Injection (, XBJ) on survival rate and pulmonary vasopermeability in a rat model of severe scald injury. METHODS: Rats were divided into two experiments: experiment 1 was monitored for 12 h post-injury for survival analysis after severe burns; in experiment 2, rats were killed for determination of pulmonary vascular permeability and pro-inflflammatory mediators. In both experiments, rats were subject to third-degree 50% total body surface area (TBSA) burns or sham injury followed by XBJ or normal saline (NS) treatment...
May 11, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28486498/migratory-phase-of-litomosoides-sigmodontis-filarial-infective-larvae-is-associated-with-pathology-and-transient-increase-of-s100a9-expressing-neutrophils-in-the-lung
#17
Gregory Karadjian, Frédéric Fercoq, Nicolas Pionnier, Nathaly Vallarino-Lhermitte, Emilie Lefoulon, Adélaïde Nieguitsila, Sabine Specht, Leo M Carlin, Coralie Martin
Filarial infections are tropical diseases caused by nematodes of the Onchocercidae family such as Mansonella perstans. The infective larvae (L3) are transmitted into the skin of vertebrate hosts by blood-feeding vectors. Many filarial species settle in the serous cavities including M. perstans in humans and L. sigmodontis, a well-established model of filariasis in mice. L. sigmodontis L3 migrate to the pleural cavity where they moult into L4 around day 9 and into male and female adult worms around day 30. Little is known of the early phase of the parasite life cycle, after the L3 is inoculated in the dermis by the vector and enters the afferent lymphatic vessels and before the moulting processes in the pleural cavity...
May 9, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28482051/biomarkers-of-chronic-acrolein-inhalation-exposure-in-mice-implications-for-tobacco-product-induced-toxicity
#18
Daniel J Conklin, Marina V Malovichko, Iris Zeller, Trinath P Das, Tatiana V Krivokhizhina, Blake H Lynch, Pawel Lorkiewicz, Abhinav Agarwal, Nalinie Wickramasinghe, Petra Haberzettl, Srinivas D Sithu, Jasmit Shah, Timothy E O'Toole, Shesh N Rai, Aruni Bhatnagar, Sanjay Srivastava
Exposure to tobacco smoke, which contains several harmful and potentially harmful constituents such as acrolein increases cardiovascular disease (CVD) risk. Although high acrolein levels induce pervasive cardiovascular injury, the effects of low-level exposure remain unknown and sensitive biomarkers of acrolein toxicity have not been identified. Identification of such biomarkers is essential to assess the toxicity of acrolein present at low levels in the ambient air or in new tobacco products such as e-cigarettes...
May 8, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28473326/reduced-carboxylesterase-1-is-associated-with-endothelial-injury-in-methamphetamine-induced-pulmonary-arterial-hypertension
#19
Mark E Orcholski, Artyom Khurshudyan, Elya A Shamskhou, Ke Yuan, Ian Y Chen, Sean D Kodani, Christophe Morisseau, Bruce D Hammock, Ellen M Hong, Ludmila Alexandrova, Tero-Pekka Alastalo, Gerald Berry, Roham T Zamanian, Vinicio A de Jesus Perez
Pulmonary arterial hypertension is a complication of methamphetamine use (METH-PAH) but the pathogenic mechanisms are unknown. Given that cytochrome P450 2D6 (CYP2D6) and carboxylesterase 1 (CES1) are involved in metabolism of METH and other amphetamine-like compounds, we postulated that loss of function variants could contribute to METH-PAH. While no difference in CYP2D6 expression was seen by lung immunofluorescence, CES1 expression was significantly reduced in endothelium of METH-PAH microvessels. Mass spectrometry analysis showed that healthy pulmonary microvascular endothelial cells (PMVECs) have the capacity to both internalize and metabolize METH...
May 4, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28463231/disruption-of-lineage-specification-in-adult-pulmonary-mesenchymal-progenitor-cells-promotes-microvascular-dysfunction
#20
Christa F Gaskill, Erica J Carrier, Jonathan A Kropski, Nathaniel C Bloodworth, Swapna Menon, Robert F Foronjy, M Mark Taketo, Charles C Hong, Eric D Austin, James D West, Anna L Means, James E Loyd, W David Merryman, Anna R Hemnes, Stijn De Langhe, Timothy S Blackwell, Dwight J Klemm, Susan M Majka
Pulmonary vascular disease is characterized by remodeling and loss of microvessels and is typically attributed to pathological responses in vascular endothelium or abnormal smooth muscle cell phenotypes. We have challenged this understanding by defining an adult pulmonary mesenchymal progenitor cell (MPC) that regulates both microvascular function and angiogenesis. The current understanding of adult MPCs and their roles in homeostasis versus disease has been limited by a lack of genetic markers with which to lineage label multipotent mesenchyme and trace the differentiation of these MPCs into vascular lineages...
June 1, 2017: Journal of Clinical Investigation
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