A novel antiapoptotic role for alpha1-antitrypsin in the prevention of pulmonary emphysema

American Journal of Respiratory and Critical Care Medicine
Irina PetracheRubin M Tuder

Abstract

There is growing evidence that alveolar cell apoptosis plays an important role in emphysema pathogenesis, a chronic inflammatory lung disease characterized by alveolar destruction. The association of alpha1-antitrypsin deficiency with the development of emphysema has supported the concept that protease/antiprotease imbalance mediates cigarette smoke-induced emphysema. We propose that, in addition to its antielastolytic effects, alpha1-antitrypsin may have broader biological effects in the lung, preventing emphysema through inhibition of alveolar cells apoptosis. METHODS, MEASUREMENTS, AND MAIN RESULTS: Transduction of human alpha1-antitrypsin via replication-deficient adeno-associated virus attenuated airspace enlargement and emphysema caused by inhibition of vascular endothelial growth factor (VEGF) receptors with SU5416 in mice, a model of apoptosis-dependent emphysema lacking neutrophilic inflammation. The overexpressed human serine protease inhibitor accumulated in lung cells and suppressed caspase-3 activation and oxidative stress in lungs treated with the VEGF blocker or with VEGF receptor-1 and -2 antibodies. Similar results were obtained in SU5416-treated rats given human alpha1-antitrypsin intravenously. Our findings s...Continue Reading

References

Apr 1, 1992·Experimental and Molecular Pathology·C GardiG Lungarella
Jan 1, 1991·Annals of the New York Academy of Sciences·C GardiG Lungarella
Mar 1, 1996·Current Opinion in Pulmonary Medicine·H P Wiedemann, J K Stoller
Nov 25, 1998·Proceedings of the National Academy of Sciences of the United States of America·S SongT R Flotte
Dec 6, 2000·The Journal of Clinical Investigation·Y KasaharaN F Voelkel
Feb 17, 2001·American Journal of Respiratory and Critical Care Medicine·A J SandfordP D Paré
May 15, 2001·American Journal of Physiology. Lung Cellular and Molecular Physiology·I PetracheJ G Garcia
Sep 11, 2001·American Journal of Respiratory and Critical Care Medicine·E CavarraG Lungarella
Feb 20, 2002·Trends in Biochemical Sciences·Henning R StennickeGuy S Salvesen
Nov 5, 2002·Methods : a Companion to Methods in Enzymology·Sergei ZolotukhinRichard O Snyder
Feb 26, 2003·American Journal of Respiratory Cell and Molecular Biology·Rubin M TuderSonia C Flores
Apr 12, 2003·American Journal of Respiratory and Critical Care Medicine·Andrew ChurgJoanne L Wright
Apr 23, 2003·American Journal of Respiratory Cell and Molecular Biology·Rubin M TuderPeter M Henson
Oct 3, 2003·American Journal of Respiratory and Critical Care Medicine·UNKNOWN American Thoracic Society, UNKNOWN European Respiratory Society
Oct 14, 2003·Biochemical Pharmacology·Catherine Stenson-CoxAfshin Samali
Apr 13, 2004·American Heart Journal·Franklin D LowyUNKNOWN National Heart, Lung and Blood Institute-National Institute of Allergy and Infectious Diseases working group on antimicrobia
Apr 20, 2004·Journal of Cellular Biochemistry·Yabing ChenDavid J Schneider
Jul 30, 2004·American Journal of Respiratory and Critical Care Medicine·Alexei GuerassimovManuel G Cosio
Oct 27, 2004·American Journal of Respiratory and Critical Care Medicine·Steven D ShapiroEdwin K Silverman
Nov 3, 2004·The Journal of Clinical Investigation·Tirumalai RangasamyShyam Biswal
Feb 22, 2005·American Journal of Respiratory Cell and Molecular Biology·Sharon A McGrath-MorrowRubin M Tuder
Jun 10, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tao ZhengJack A Elias

❮ Previous
Next ❯

Citations

Jun 4, 2010·Pathology Oncology Research : POR·Aleksandra TopicDragica Radojkovic
Mar 8, 2013·Nature Reviews. Cancer·A McGarry Houghton
Oct 15, 2008·Proceedings of the National Academy of Sciences of the United States of America·Maria KoulmandaTerry B Strom
Sep 6, 2012·Proceedings of the National Academy of Sciences of the United States of America·Maria KoulmandaTerry B Strom
May 9, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sadaf SohrabIrina Petrache
Feb 7, 2012·American Journal of Physiology. Lung Cellular and Molecular Physiology·Mark T KearnsR William Vandivier
Jun 5, 2007·American Journal of Respiratory and Critical Care Medicine·Klaus F RabeLeonardo M Fabbri
Dec 17, 2009·American Journal of Respiratory and Critical Care Medicine·Ali O YildirimHeinz Fehrenbach
Dec 8, 2009·American Journal of Respiratory and Critical Care Medicine·Khalil J DiabIrina Petrache
Mar 31, 2007·American Journal of Respiratory Cell and Molecular Biology·Andrew ChurgJoanne L Wright
Jun 2, 2007·American Journal of Respiratory Cell and Molecular Biology·Rubin M Tuder, Irina Petrache
Apr 29, 2008·American Journal of Respiratory Cell and Molecular Biology·Rubin M TuderBrian B Graham
Jan 27, 2009·American Journal of Respiratory Cell and Molecular Biology·Julie NoeIrina Petrache
Jan 10, 2009·American Journal of Respiratory Cell and Molecular Biology·Ahmed LazrakSadis Matalon
May 8, 2010·American Journal of Respiratory Cell and Molecular Biology·Rachel DamicoPaul M Hassoun
Mar 26, 2013·American Journal of Respiratory Cell and Molecular Biology·Angelia D LockettIrina Petrache
Mar 26, 2013·American Journal of Respiratory Cell and Molecular Biology·Megan P StogsdillPaul R Reynolds
Feb 5, 2008·The Journal of Clinical Investigation·Laimute Taraseviciene-Stewart, Norbert F Voelkel
Dec 30, 2009·The Journal of Clinical Investigation·Andrew A WilsonDarrell N Kotton
Apr 14, 2011·Orphanet Journal of Rare Diseases·Ignacio BlancoFrederick de Serres
Feb 7, 2009·Journal of Leukocyte Biology·Gregory B PottLeland Shapiro
Apr 20, 2014·PloS One·Angelia D LockettIrina Petrache
Aug 22, 2006·Proceedings of the American Thoracic Society·Rubin M TuderIrina Petrache
Oct 27, 2006·Proceedings of the American Thoracic Society·Rubin M TuderIrina Petrache
May 6, 2008·Proceedings of the American Thoracic Society·Craig P HershEdwin K Silverman
Oct 30, 2010·Proceedings of the American Thoracic Society·Rubin M TuderIrina Petrache
Nov 5, 2011·Proceedings of the American Thoracic Society·Rubin M Tuder, Toshinori Yoshida
May 29, 2012·Molecular Medicine·Eli C Lewis
Oct 25, 2013·International Journal of Medical Sciences·Yusuke TakahashiHiroaki Nomori
Apr 17, 2014·American Journal of Respiratory and Critical Care Medicine·Ignacio Blanco
May 3, 2014·American Journal of Respiratory Cell and Molecular Biology·Juan-Antonio MorenoOlivier Meilhac
Aug 27, 2009·Biologics : Targets & Therapy·Caitriona McLeanNoel G McElvaney
Jan 20, 2015·Expert Review of Respiratory Medicine·Alessandro N FranciosiNoel Gerry McElvaney
Dec 5, 2015·Expert Review of Respiratory Medicine·Killian HurleyNoel G McElvaney

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell-Type Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Cell-Type-Specific Viral Vectors (ASM)

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Cell-Type-Specific Viral Vectors

Viral vectors are used in biological research and therapy to deliver genetic material into cells. However, the efficiency of viral vectors varies depending on the cell type. Here is the latest research on cell-type-specific viral vectors.

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

American Thoracic Association Journals

Discover the latest respiratory research published by the journals from the American Thoracic Society.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Cardiomegaly

Cardiomegaly, known as an enlarged heart, is a multifactorial disease with different pathophysiological mechanisms. Hypertension, pregnancy, exercise-induced and idiopathic causes are some mechanisms of cardiomegaly. Discover the latest research of cardiomegaly here.

© 2021 Meta ULC. All rights reserved