Proteases in Tissue Remodelling of Lung And Heart PDF
Preview Proteases in Tissue Remodelling of Lung And Heart
PROTEASES IN TISSUE REMODELLING OF LUNG AND HEART PROTEASES IN BIOLOGY AND DISEASE SERIES EDITORS: NIGEL M.HOOPER.University ofLeeds.Leeds, United Kingdom UWE LENDECKEL,Otto-von-Guericke University.Magdeburg,Germany Volume1 PROTEASES INTISSUE REMODELLING OFLUNG AND HEART Edited by Uwe Lendeckel and Nigel M. Hooper AContinuationOrderPlanisavailableforthisseries.Acontinuationorderwillbringdeliveryofeach newvolumeimmediatelyuponpublication.Volumesarebilledonlyuponactualshipment.Forfurther information please contact the publisher. PROTEASES IN TISSUE REMODELLING OF LUNG AND HEART Edited by Uwe Lendeckel Otto-von-Guericke University Magdeburg. Germany and Nigel M. Hooper UniversityofLeeds Leeds. UnitedKingdom Kluwer Academic / Plenum Publishers New York, Boston, Dordrecht, London, Moscow ISBN0-306-47910-9 ©2003 Kluwer Academic/Plenum Publishers, New York 233Spring Street,New York,New York10013 http://www.wkap.nV 10 9 8 7 6 5 4 3 2 I Ac.I.P.record forthis book isavailable from the Library ofCongress All rights reserved No partof this book maybe reproduced,stored inaretrieval system, or transmitted inany form or by any means,electronic, mechanical, photocopying, microfilming,recording,orotherwise, without written permission from the Publisher, with theexception ofany material supplied specifically forthe purpose of being entered andexecuted on acomputersystem,forexclusive usebythe purchaser of the work. Permissions forbooks published inEurope: [email protected] Permissions for books published inthe United States of America:permissionstiswkap.com Printed inthe United States of America Preface Withsome2%ofthe humangenomeencodingforproteases itisperhaps not too surprising to fmd that proteases are involved in a wide range of biological processes, including angiogenesis, antigen processing, cell cycle regulation,cellgrowth anddifferentiation,embryogenesis anddevelopment, fertilisation and reproduction, and tissue remodelling. In tum, this means thatnumerous disease states such as arthritis, cancer and inflammation, are dueto abnormal protease activity and that either inhibition orup-regulation of protease activity may be viable therapeutic approaches. The aim ofthis book is to highlight the role ofproteases in tissue remodelling of the lung andheart.Inevitably, withthekey roleplayed bythe extracellular matrix in these processes, a number of the chapters focus on the role of matrix metalloprotease(MMP) familymemberssuchascollagenase,gelatinase and stromelysin that together can effectively degrade the extracellular matrix. However, the role of other proteases, including cathepsins, the calcium dependent calpains, caspases, a disintegrin and metalloprotease (ADAM) family of proteases and a number of cell-surface peptidases such as angiotensin converting enzyme, dipeptidyl peptidase IV, aminopeptidases and carboxypeptidases, neprilysin and endothelin converting enzyme are also covered where appropriate. The first half of this volume covers the roles of proteases in remodelling of the lung, with the second half addressingtheirroleinremodellingoftheheart. Cystic fibrosis, caused by a defect in the cystic fibrosis transmembrane conductanceregulator (CFTR), isthe mostcommon fatal disease caused by a single gene defect in Europe and North America. Chapter I by Andre Cantin, Amelie Fournier and Richard Leduc explores the potential links betweendeficiency ofthe CFTRprotein,·lung infection, neutrophils and the v vi PREFACE role of human leukocyte elastase and its natural inhibitors in the pathophysiologyof cystic fibrosis. In chapter 2, YvesSt.Pierre and Celine VanThemsche focus attention on how expression of different members of the MMP family is regulated and how these proteases intervene during inflammatory lung disorders. In chapter 3, A. Wille, T. Welte and F. Biihlingdescribethe role ofMMPs andcathepsinsinthe degradationofthe pulmonary extracellular matrix, the common end point of a range of interstitial lung diseases such as idiopathic pulmonary fibrosis, granulomatouslungdiseases, acute lunginjuryandasthma.Theyalsotouch on the role of specific inhibitors of the MMPs, the tissue inhibitors of metalloproteinases (TIMPs) and of the cysteine proteases, the cystatins, which serve to keep these proteases in check under normal circumstances. Pulmonaryemphysema, permanent abnormal enlargementof the peripheral air spaces of the lungs, is a major component of chronic obstructive pulmonary diseases. In chapter 4, Thomas Purcell and Manuel Hidalgo outline the principal rationale for targeting the MMPs therapeutically and provide a comprehensive review of the drugs currently in clinical trials for solid tumours including small-cell and non-small cell lung cancer. In chapter 5, Heiko Golpon, Thomas Kohnlein and Tobias Welte describe the role of proteases in this process and outline the apoptosis-initiated model leadingto pulmonary emphysema.MMPsplaya criticalrole inthe process of tumour growth, invasion and metastasis, and as a result a number of MMPinhibitorsareundergoingevaluationinclinicaltrials. Increased MMP activity is one reason for an imbalance between inhibitors and stimulators of collagen turnover. In chapter 6, Ute Seeland and Michael Bohm discuss the role of MMPs in cardiac remodeling in pressure overload hypertrophy, focusingonthe complexity of extracellular signals that influence the biological behaviour of myocardial fibroblasts. MMPfamilymembers are overexpressedinthe myocardiuminbothanimal and human myocardial pathophysiology, including myocardial infarction, cardiomyopathyandheart failure.In chapter 7,TomosaburoTakahashi and Richard Lee review the recent evidence for the involvement of MMPs as potential mediators of cardiac remodelling and progression to heart failure and that MMP inhibition may be a potential strategy for preventing heart failure. Left ventricular dilation and remodeling contribute to the progressionofchronic heartfailureandhavebeenassociatedwithincreased morbidity and mortality. In chapter 8, Yun You Li and Arthur Feldman describe the role of MMPs in myocardial remodelling in heart failure and howmodulation of MMP activity could be used to alter the progression of the disorder. The activation of different extra- and intracellular proteases has a significant impact on remodelling of cardiac tissue. In chapter 9, Andreas Goette, Christoph Rocken, Karen Nepple and Uwe Lendeckel PREFACE vii describe the role ofa number of different proteases, including the calpains, caspases, various ectopeptidases, MMPs and ADAMsinthedevelopmentof cardiac arrhythmias. These authors also comment on how specific protease inhibitors may help to improve the "classic antiarrhythmic approach" consisting of ion channel blockers. The last chapter by Heike Mertsching and Carmen Puschmann describes the impact of proteases, particularly MMPs, intissue engineering andregeneration. Finally, we would like to thank all the authors for their scholarly and timely contributions and apologize to them for editorial changes in the interestsofconsistency andclarity. U.LendeckelandN.M.Hooper May2003 Contributors Bohm, Michael DirektorderKlinik InnereMedizin III(Kardiologie/Angiologie) Universitatsklinikendes Saarlandes KirrbergerStr. 66421 Homburg!Saar,Denmark e-mail:[email protected] Biihling, Frank Otto-von-Guericke-UniversitatMagdeburg Institutfur Imrnunologie LeipzigerStr. 44 D-39120Magdeburg,Germany e-mail: [email protected] Cantin,Andre M. Universitede Sherbrooke PulmonologyDivision,Dept. Medicine 3001, 12e Avenue Nord Sherbrooke (Quebec),CanadaJlH5N4 e-mail: [email protected] ix x CONTRIBUTORS Feldman,ArthurM. Dept. ofMedicine Jefferson Medical College 1025WalnutStreet Philadelphia,PA 19107,USA e-mail: [email protected] Fournier,Amelie PulmonologyDivision,Faculty ofMedicine University ofSherbrooke 3001, 12eAvenue N Sherbrooke, QC JIH 5N4, Canada e-mail:[email protected] Goette, Andreas Otto-von-Guericke-UniversitatMagdeburg Klinik fur Kardiologie,Angiologie und Pneumologie D-39120Magdeburg,Germany e-mail: [email protected] Golpon, Heiko Otto-von-Guericke-UniversitatMagdeburg Abt. PneumologieundIntensivmedizin LeipzigerStr.44 39120 Magdeburg,Germany e-mail:[email protected] Hidalgo, Manuel AssociateProfessorofOncology The Johns Hopkins UniversitySchool ofMedicine co-DirectorDrug DevelopmentProgram The Sidney Kimmel Comprehensive CancerCenteratJohns Hopkins 1650Orleans St.Room IM88 Baltimore,MD,21231-1000, USA e-mail: [email protected] Kohnlein,Thomas Otto-von-Guericke-UniversitatMagdeburg Abt. PneumologieundIntensivmedizin LeipzigerStr. 44 D-39120Magdeburg, Germany e-mail: [email protected] CONTRIBUTORS xi Leduc,Richard Department ofPharmacology Faculty ofMedicine University ofSherbrooke 3001, 12eAvenue N,room Z5-1006 Sherbrooke, QC JIH 5N4, Canada e-mail:[email protected] Lee, Richard T. CardiovascularDivision BrighamandWomen's Hospital Harvard Medical School PartnersResearch Facility, R289 65LandsdowneStreet Cambridge, MA 02139, USA e-mail: [email protected] Lendeckel,Uwe Otto-von-Guericke-UniversitatMagdeburg Institut fur ExperimentelleInnere Medizin LeipzigerStr.44 D-39120Magdeburg,Germany e-mail: [email protected] Li, Yun You Dept. ofInternal Medicine UPMC Shadyside Room 215 SON 5230 Centre Ave Pittsburgh,PA 15232,USA e-mail: [email protected] Mertsching,Heike LEBAO imFZder MHH Podbielskistr. 380 30659 Hannover, Germany email: [email protected]
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