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https://www.readbyqxmd.com/read/28202489/nicotinamide-phosphoribosyltransferase-promotes-pulmonary-vascular-remodeling-and-is-a-therapeutic-target-in-pulmonary-arterial-hypertension
#1
Jiwang Chen, Justin R Sysol, Sunit Singla, Shuangping Zhao, Aya Yamamura, Daniela Valdez-Jasso, Taimur Abbasi, Krystyna M Shioura, Sakshi Sahni, Vamsi Reddy, Arvind Sridhar, Hui Gao, Jaime Torres, Sara M Camp, Haiyang Tang, Shui Quing Ye, Suzy Comhair, Raed Dweik, Paul Hassoun, Jason X-J Yuan, Joe G N Garcia, Roberto F Machado
Background -Pulmonary arterial hypertension (PAH) is a severe and progressive disease, a hallmark of which is pulmonary vascular remodeling. Nicotinamide phosphoribosyltransferase (NAMPT), is a cytozyme which regulates intracellular NAD levels and cellular redox state, regulates histone deacetylases, promotes cell proliferation and inhibits apoptosis. We hypothesized that NAMPT promotes pulmonary vascular remodeling, and that inhibition of NAMPT could attenuate pulmonary hypertension. Methods -Plasma and mRNA and protein levels of NAMPT were measured in the lungs and isolated pulmonary artery endothelial cells (PAECs) from PAH patients, as well as in lungs of rodent models of pulmonary hypertension (PH)...
February 15, 2017: Circulation
https://www.readbyqxmd.com/read/28185902/lung-remodeling-in-aging-surfactant-protein-d-deficient-mice
#2
Jan Philipp Schneider, Martina Arkenau, Lars Knudsen, Dirk Wedekind, Matthias Ochs
Pulmonary surfactant, a mixture of lipids and proteins at the air-liquid interface of alveoli, prevents the lungs from collapsing due to surface tension. One constituent is surfactant-associated protein-D (SP-D), a protein involved in surfactant homeostasis and innate immunity. Mice deficient in SP-D (SP-D (-/-)) have been described as developing a characteristic phenotype which affects the surfactant system (including changes in the intra-cellular and intra-alveolar surfactant pool, alveolar epithelial type II cells and alveolar macrophages), lung architecture and its inflammatory state (development of an emphysema-like pathology, inflammatory cell infiltration)...
February 6, 2017: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
https://www.readbyqxmd.com/read/28174048/the-effects-of-particulate-matter-on-inflammation-of-respiratory-system-differences-between-male-and-female
#3
Kelly Yoshizaki, Jôse Mára Brito, Luiz Fernando Silva, Adriana Lino-Dos-Santos-Franco, Daniela Perroni Frias, Renata Calciolari Rossi E Silva, Luís Fernando Amato-Lourenço, Paulo Hilário Nascimento Saldiva, Iolanda de Fátima Lopes Calvo Tibério, Thais Mauad, Mariangela Macchione
Air pollution is known to exacerbate respiratory diseases and epidemiological studies have shown that women present more chronic respiratory symptoms than man exposed to traffic pollution, however, the reason why is unclear. This study evaluated the inflammatory differences in BALB/c mouse males (n=34) and females (n=111) in three phases of the estrous cycle that were exposed to ambient air (AA) or concentrated ambient particles (CAPs). Tracheal hyperreactivity to methacholine, bronchoalveolar lavage fluid (BALF) and immunohistochemical of airways and lung parenchyma were studied...
February 4, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28162182/-therapeutic-effects-of-histone-deacetylase-inhibitor-givinostat-on-air-inflammation-and-high-airway-resistance-in-a-murine-asthma-model
#4
X M Su, Y Ren, L F Kong, J Kang
Objective: To investigate the therapeutic effects of givinostat, a histone deacetylase inhibitor (HDACI), on the development of chronic asthma with airway inflammation, airway remodeling and airway hyperresponsiveness (AHR). Methods: BALB/C mice were randomly divided into control group, asthma group, dexamethasone group and givinostat group (n=12 per group). AHR was assessed. Total cell numbers and differential counts, interleukin-4(IL-4), interleukin-5(IL-5) and interferon-γ (IFNγ) levels in the bronchoalveolar lavage fluid (BALF) were measured in the above 4 groups...
February 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/28148930/mir-126a-5p-is-involved-in-the-hypoxia-induced-endothelial-to-mesenchymal-transition-of-neonatal-pulmonary-hypertension
#5
Yan-Ping Xu, Qi He, Zheng Shen, Xiao-Li Shu, Chen-Hong Wang, Jia-Jun Zhu, Li-Ping Shi, Li-Zhong Du
Persistent pulmonary hypertension of the newborn (PPHN) is a clinical syndrome characterized by increased medial and adventitial thickness of the lung vasculature. The underlying mechanisms that regulate the cell phenotype alteration during PPHN remodeling are largely unknown. We randomly selected newborn rats that were exposed to hypoxia (10-12%) or room air for 2 weeks and used a microarray to identify the lung tissue microRNAs (miRNAs) involved in PPHN progression. The role of a key miRNA that affects the endothelial-to-mesenchymal transition (EndMT) in primary cultured rat pulmonary microvascular endothelial cells (RPMECs) was investigated...
February 2, 2017: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/28124622/intermittent-hypoxia-causes-nox2-dependent-remodeling-of-atrial-connexins
#6
Joanna Gemel, Zihan Su, Alex Gileles-Hillel, Abdelnaby Khalyfa, David Gozal, Eric C Beyer
BACKGROUND: Obstructive sleep apnea has been linked to the development of heart disease and arrhythmias, including atrial fibrillation. Since altered conduction through gap junction channels can contribute to the pathogenesis of such arrhythmias, we examined the abundance and distributions of the major cardiac gap junction proteins, connexin40 (Cx40) and connexin43 (Cx43) in mice treated with sleep fragmentation or intermittent hypoxia (IH) as animal models of the components of obstructive sleep apnea...
January 17, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/28088960/-role-and-mechanism-of-hydrogen-sulfide-in-cigarette-smoke-induced-chronic-obstructive-pulmonary-disease-related-pulmonary-vascular-remodeling-in-rats
#7
M X Li, Y H Chen, C C Liao, F Lin, Y Bai, W J Mi, Y Sun, Y F Qi
Objective: To investigate the role and mechanism of hydrogen sulfide (H2S) in rats with chronic obstructive pulmonary disease (COPD) related pulmonary vascular remodeling. Methods: Twenty four healthy male Sprague-Dawley rats were randomly divided into 4 groups: control group, cigarette smoke (CS) group, CS+ Sodium hydrosulfide (NaHS) group and CS+ DL-propargylglycine (PPG) group. Rats in control group were fed normally and breathed clear air, and for the rest groups, passive cigarette smoke inhalation method were adopted to establish COPD model...
January 10, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28059551/wnt-signaling-in-chronic-rhinosinusitis-with-nasal-polyps
#8
Robert Böscke, Eszter K Vladar, Michael Könnecke, Birgit Hüsing, Robert Linke, Ralph Pries, Norbert Reiling, Jeffrey D Axelrod, Jayakar V Nayak, Barbara Wollenberg
The signaling pathways that sustain the disease process of chronic rhinosinusitis with nasal polyps (CRSwNP) remain poorly understood. We sought to determine the expression levels of Wnt signaling genes in CRSwNP, and to study the role of the Wnt pathway in inflammation and epithelial remodeling in the nasal mucosa. Microarrays and RT-qPCR comparing gene expression in matched nasal polyps (NP) and inferior turbinates (IT) revealed that WNT2B, WNT3A, WNT4, WNT7A, WNT7B and FZD2 were upregulated, and FZD1, LRP5, LRP6 and WIF1 downregulated in NPs...
January 6, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28013306/inhibition-of-rac1-signaling-downregulates-inflammasome-activation-and-attenuates-lung-injury-in-neonatal-rats-exposed-to-hyperoxia
#9
Julia K Hummler, Fredrick Dapaah-Siakwan, Ruben Vaidya, Ronald Zambrano, Siwei Luo, Shaoyi Chen, Nadine Kerr, Juan Pablo de Rivero Vaccari, Robert W Keane, W Dalton Dietrich, Eduardo Bancalari, Karen C Young, Shu Wu
BACKGROUND: Inflammatory injury, particularly the production of active interleukin (IL)-1β plays a major role in the pathogenesis of bronchopulmonary dysplasia (BPD) in preterm infants. The release of active IL-1β is controlled by posttranscriptional modifications of its proform (pro-IL-1β) through the inflammasome. Rac1 is a member of the Rho family of GTPases that regulate the inflammatory process. OBJECTIVE: This study tested the hypothesis that Rac1 signaling increases inflammasome activation that results in damaging inflammation, and that the inhibition of Rac1 signaling prevents lung injury, by inhibiting inflammasome activation in a newborn rat model of BPD induced by hyperoxia...
December 24, 2016: Neonatology
https://www.readbyqxmd.com/read/27990700/biomass-fuel-smoke-exposure-was-associated-with-adverse-cardiac-remodeling-and-left-ventricular-dysfunction-in-peru
#10
Melissa S Burroughs Peña, Eric J Velazquez, Jose D Rivera, Fawaz Alenezi, Catherine Wong, Matthew Grigsby, Victor G Davila-Roman, Robert H Gilman, Jaime J Miranda, William Checkley
BACKGROUND: While household air pollution from biomass fuel combustion has been linked to cardiovascular disease, the effects on cardiac structure and function have not been well described. We sought to determine the association between biomass fuel smoke exposure and cardiac structure and function by transthoracic echocardiography. METHODS: We identified a random sample of urban and rural residents living in the high-altitude region of Puno, Peru. Daily biomass fuel use was self-reported...
December 19, 2016: Indoor Air
https://www.readbyqxmd.com/read/27897352/functional-magnetic-resonance-imaging-for-in-vivo-quantification-of-pulmonary-hypertension-in-the-sugen-5416-hypoxia-mouse
#11
Ellen C Breen, Miriam Scadeng, N Chin Lai, Fiona Murray, Timothy D Bigby
Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary artery pressures and right heart failure. PAH mouse models are instrumental in understanding disease pathophysiology. However, few methods are available to evaluate right cardiac function in small animals. In this study, magnetic resonance imaging (MRI) was used to measure in vivo cardiac dimensions in the Sugen 5416/hypoxia mouse model. Pulmonary hypertension (PH) was induced in C57BL/6 mice by three weeks of exposure to 10% oxygen and VEGF receptor inhibition (20 mg kg(-1) SU5416)...
November 29, 2016: Experimental Physiology
https://www.readbyqxmd.com/read/27878968/proprotein-convertase-inhibition-promotes-ciliated-cell-differentiation-a-potential-mechanism-for-the-inhibition-of-notch1-signalling-by-decanoyl-rvkr-chloromethylketone
#12
Sang-Nam Lee, In-Suk Choi, Hyun Jun Kim, Eun Jin Yang, Hyun Jin Min, Joo-Heon Yoon
Chronic repetitive rounds of injury and repair in the airway lead to airway remodelling, including ciliated cell loss and mucous cell hyperplasia. Airway remodelling is mediated by many growth and differentiation factors including Notch1, which are proteolytically processed by proprotein convertases (PCs). The present study evaluated a novel approach for controlling basal cell-type determination based on the inhibition of PCs. It was found that decanoyl-RVKR-chloromethylketone (CMK), a PC inhibitor, promotes ciliated cell differentiation and has no effect on the ciliary beat frequency in air-liquid interface (ALI) cultures of human nasal epithelial cells (HNECs)...
November 22, 2016: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/27860185/sildenafil-attenuates-hypoxic-pulmonary-remodelling-by-inhibiting-bone-marrow-progenitor-cells
#13
Shirley Favre, Elisa Gambini, Patrizia Nigro, Alessandro Scopece, Paola Bianciardi, Anna Caretti, Giulio Pompilio, Antonio F Corno, Giuseppe Vassalli, Ludwig K von Segesser, Michele Samaja, Giuseppina Milano
The recruitment of bone marrow (BM)-derived progenitor cells to the lung is related to pulmonary remodelling and the pathogenesis of pulmonary hypertension (PH). Although sildenafil is a known target in PH treatment, the underlying molecular mechanism is still elusive. To test the hypothesis that the therapeutic effect of sildenafil is linked to the reduced recruitment of BM-derived progenitor cells, we induced pulmonary remodelling in rats by two-week exposure to chronic hypoxia (CH, 10% oxygen), a trigger of BM-derived progenitor cells...
November 18, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27783217/lung-surfactant-metabolism-early-in-life-early-in-disease-and-target-in-cell-therapy
#14
REVIEW
Elena Lopez-Rodriguez, Gemma Gay-Jordi, Adele Mucci, Nico Lachmann, Anna Serrano-Mollar
Lung surfactant is a complex mixture of lipids and proteins lining the alveolar epithelium. At the air-liquid interface, surfactant lowers surface tension, avoiding alveolar collapse and reducing the work of breathing. The essential role of lung surfactant in breathing and therefore in life, is highlighted by surfactant deficiency in premature neonates, which causes neonatal respiratory distress syndrome and results in early death after birth. In addition, defects in surfactant metabolism alter lung homeostasis and lead to disease...
October 25, 2016: Cell and Tissue Research
https://www.readbyqxmd.com/read/27768904/gill-remodelling-and-growth-rate-of-striped-catfish-pangasianodon-hypophthalmus-under-impacts-of-hypoxia-and-temperature
#15
Le My Phuong, Do Thi Thanh Huong, Jens Randel Nyengaard, Mark Bayley
Gill morphometric and gill plasticity of the air-breathing striped catfish (Pangasianodon hypophthalmus) exposed to different temperatures (present day 27°C and future 33°C) and different air saturation levels (92% and 35%) during 6weeks were investigated using vertical sections to estimate the respiratory lamellae surface areas, harmonic mean barrier thicknesses, and gill component volumes. Gill respiratory surface area (SA) and harmonic mean water - blood barrier thicknesses (HM) of the fish were strongly affected by both environmental temperature and oxygen level...
January 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/27763528/up-regulation-of-claudin-6-in-the-distal-lung-impacts-secondhand-smoke-induced-inflammation
#16
Joshua B Lewis, Dallin C Milner, Adam L Lewis, Todd M Dunaway, Kaleb M Egbert, Scott C Albright, Brigham J Merrell, Troy D Monson, Dallin S Broberg, Jason R Gassman, Daniel B Thomas, Juan A Arroyo, Paul R Reynolds
It has long been understood that increased epithelial permeability contributes to inflammation observed in many respiratory diseases. Recently, evidence has revealed that environmental exposure to noxious material such as cigarette smoke reduces tight junction barrier integrity, thus enhancing inflammatory conditions. Claudin-6 (Cldn6) is a tetraspanin transmembrane protein found within the tight junctional complex and is implicated in maintaining lung epithelial barriers. To test the hypothesis that increased Cldn6 ameliorates inflammation at the respiratory barrier, we utilized the Tet-On inducible transgenic system to conditionally over-express Clnd6 in the distal lung...
October 17, 2016: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/27713609/secondhand-smoke-exposure-enhances-cardiac-fibrosis-effects-on-the-aging-rat-hearts
#17
Jia-Ping Wu, Shu Nu Chang-Lee, Cecilia Hsuan Day, Tsung-Jung Ho, Vijaya Padma Viswanadha, Li-Chin Chung, Jin-Ming Hwang, Gwo-Ping Jong, Wei-Wen Kuo, Chih-Yang Huang
BACKGROUND: Examining aging rats exposed to secondhand smoke (SHS) engenders changes in left ventricular remodeling due to age- or disease-dependent alterations. METHODS: Rats were placed in whole-body exposure chambers and exposed to 10 cigarettes. Filtered air was introduced into the chamber at a low rate. Rats were exposed to SHS for 30 min, twice a day, 5 days per week for 1 month. After 4 weeks SHS exposure, rats were sacrificed for morphological study with trichome staining and left ventricular remodeling related protein analysis using western blot...
September 2016: Acta Cardiologica Sinica
https://www.readbyqxmd.com/read/27703346/inhaled-corticosteroid-normalizes-some-but-not-all-airway-vascular-remodeling-in-copd
#18
Amir Soltani, Eugene Haydn Walters, David W Reid, Shakti Dhar Shukla, Kaosia Nowrin, Chris Ward, H Konrad Muller, Sukhwinder Singh Sohal
BACKGROUND: This study assessed the effects of inhaled corticosteroid (ICS) on airway vascular remodeling in chronic obstructive pulmonary disease (COPD). METHODS: Thirty-four subjects with mild-to-moderate COPD were randomly allocated 2:1 to ICS or placebo treatment in a double-blinded clinical trial over 6 months. Available tissue was compared before and after treatment for vessel density, and expression of VEGF, TGF-β1, and TGF-β1-related phosphorylated transcription factors p-SMAD 2/3...
2016: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/27694473/simvastatin-prevents-and-reverses-chronic-pulmonary-hypertension-in-newborn-rats-via-pleiotropic-inhibition-of-rhoa-signaling
#19
Mathew J Wong, Crystal Kantores, Julijana Ivanovska, Amish Jain, Robert P Jankov
Chronic neonatal pulmonary hypertension (PHT) frequently results in early death. Systemically administered Rho-kinase (ROCK) inhibitors prevent and reverse chronic PHT in neonatal rats, but at the cost of severe adverse effects, including systemic hypotension and growth restriction. Simvastatin has pleiotropic inhibitory effects on isoprenoid intermediates that may limit activity of RhoA, which signals upstream of ROCK. We therefore hypothesized that statin treatment would safely limit pulmonary vascular RhoA activity and prevent and reverse experimental chronic neonatal PHT via downstream inhibitory effects on pathological ROCK activity...
November 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27693345/biosurfactants-and-surfactants-interacting-with-membranes-and-proteins-same-but-different
#20
REVIEW
Daniel E Otzen
Biosurfactants (BS) are surface-active molecules produced by microorganisms. For several decades they have attracted interest as promising alternatives to current petroleum-based surfactants. Aside from their green profile, they have remarkably low critical micelle concentrations, reduce the air/water surface tension to very low levels and are excellent emulsifiers, all of which make them comparable or superior to their synthetic counterparts. These remarkable physical properties derive from their more complex chemical structures in which hydrophilic and hydrophobic regions are not as clearly separated as chemical surfactants but have a more mosaic distribution of polarity as well as branched or circular structures...
September 30, 2016: Biochimica et Biophysica Acta
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