Endothelial HIF-2α as a Key Endogenous Mediator Preventing Emphysema.

American Journal of Respiratory and Critical Care Medicine
Shravani PasupnetiMark R Nicolls

Abstract

Rationale: Endothelial injury may provoke emphysema, but molecular pathways of disease development require further discernment. Emphysematous lungs exhibit decreased expression of HIF-2α (hypoxia-inducible factor-2α)-regulated genes, and tobacco smoke decreases pulmonary HIF-2α concentrations. These findings suggest that decreased HIF-2α expression is important in the development of emphysema.Objectives: The objective of this study was to evaluate the roles of endothelial-cell (EC) HIF-2α in the pathogenesis of emphysema in mice.Methods: Mouse lungs were examined for emphysema after either the loss or the overexpression of EC Hif-2α. In addition, SU5416, a VEGFR2 inhibitor, was used to induce emphysema. Lungs were evaluated for HGF (hepatocyte growth factor), a protein involved in alveolar development and homeostasis. Lungs from patients with emphysema were measured for endothelial HIF-2α expression.Measurements and Main Results: EC Hif-2α deletion resulted in emphysema in association with fewer ECs and pericytes. After SU5416 exposure, EC Hif-2α-knockout mice developed more severe emphysema, whereas EC Hif-2α-overexpressing mice were protected. EC Hif-2α-knockout mice demonstrated lower levels of HGF. Human emphysema lung samp...Continue Reading

References

Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·G L WangG L Semenza
Oct 1, 1998·The American Journal of Physiology·A Y YuG L Semenza
Dec 6, 2000·The Journal of Clinical Investigation·Y KasaharaN F Voelkel
May 21, 2003·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·M G Belvisi, K M Bottomley
Jun 29, 2004·The European Respiratory Journal·B R CelliUNKNOWN ATS/ERS Task Force
Jul 10, 2004·Experimental Cell Research·Laura M DeBuskPengnian Charles Lin
Jul 5, 2005·American Journal of Respiratory and Critical Care Medicine·Sanna PadelaA Keith Tanswell
Mar 31, 2006·Respiratory Research·Ingel K DemedtsGuy G Brusselle
Aug 22, 2006·Proceedings of the American Thoracic Society·Rubin M TuderIrina Petrache
Oct 31, 2006·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Arnaud MonvoisinM Luisa Iruela-Arispe
Sep 4, 2007·Lancet·David M Mannino, A Sonia Buist
Mar 14, 2009·Biology of the Cell·Eric SulpiceTatyana Merkulova-Rainon
Feb 5, 2010·American Journal of Respiratory and Critical Care Medicine·Connie C W HsiaUNKNOWN ATS/ERS Joint Task Force on Quantitative Assessment of Lung Structure
Jun 22, 2010·The European Respiratory Journal·M YasuoN F Voelkel
Oct 23, 2010·Molecular Cell·Amar J MajmundarM Celeste Simon
Feb 3, 2012·American Journal of Respiratory Cell and Molecular Biology·Yadi HuangRobbert J Rottier
Jul 24, 2012·Trends in Biochemical Sciences·Mei Yee Koh, Garth Powis
Dec 25, 2012·Fibrogenesis & Tissue Repair·Volker H Haase
Nov 5, 2014·Immunity·Asis PalazonRandall S Johnson
Jun 13, 2015·American Journal of Respiratory and Critical Care Medicine·Katja HueperR Graham Barr
Mar 16, 2016·Molecular and Cellular Biology·Pinelopi P KapitsinouVolker H Haase
Apr 6, 2016·The Journal of Biological Chemistry·Andrew C SelfridgeCormac T Taylor
Jul 5, 2016·The Journal of Allergy and Clinical Immunology·Peter J Barnes
Oct 31, 2014·Biomedicines·Kunio MatsumotoKatsuya Sakai
Sep 21, 2017·The Journal of Pharmacology and Experimental Therapeutics·Jennifer L AriaziConnie Erickson-Miller
Dec 8, 2017·European Respiratory Review : an Official Journal of the European Respiratory Society·Corry-Anke BrandsmaWim Timens
Jan 18, 2018·Immunology·Jeffrey L EbersoleOctavio A Gonzalez
Jun 6, 2018·Global Health, Epidemiology and Genomics·S A Quaderi, J R Hurst
Jun 24, 2018·Nature Communications·Katsuhiro KatoRalf H Adams
Jan 10, 2019·Annual Review of Pharmacology and Toxicology·Gregg L Semenza

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Citations

Jul 17, 2020·The Journal of Clinical Investigation·Xinguo JiangMark R Nicolls
Jan 22, 2021·Stem Cells Translational Medicine·Katrina M LappinTerence R Lappin
Feb 2, 2021·Frontiers in Immunology·Xiangyun LiXiaoyi Yuan
Apr 16, 2021·American Journal of Respiratory and Critical Care Medicine·Andy I RitchieGavin C Donaldson

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