FRONTIERS IN RESEARCH OF THE RENIN-ANGIOTENSIN SYSTEM ON HUMAN DISEASE Editedby Po Sing Leung, PhD DepartmentofPhysiology, FacultyofMedicine, TheChineseUniversityofHongKong, Shatin,HongKong,China AC.I.P.CataloguerecordforthisbookisavailablefromtheLibraryofCongress. ISBN978-1-4020-6371-8(HB) ISBN978-1-4020-6372-5(e-book) PublishedbySpringer, P.O.Box17,3300AADordrecht,TheNetherlands. www.springer.com Printedonacid-freepaper AllRightsReserved ©2007Springer Nopartofthisworkmaybereproduced,storedinaretrievalsystem,ortransmitted inanyformorbyanymeans,electronic,mechanical,photocopying,microfilming,recording orotherwise,withoutwrittenpermissionfromthePublisher,withtheexception ofanymaterialsuppliedspecificallyforthepurposeofbeingentered andexecutedonacomputersystem,forexclusiveusebythepurchaserofthework. CONTENTS Preface.............................................................. vii Contributors.......................................................... ix 1 Role of ACE, ACE2 and Neprilysin in the Kidney................... 1 Mark C. Chappell 2 ACE Inhibition in Heart Failure and Ischaemic Heart Disease......... 21 Duncan J. John Campbell 3 Proteases of the Renin-Angiotensin System in Human Acute Pancreatitis................................................. 55 R. Pezzilli and L. Fantini 4 The Renin-Angiotensin System in Pancreatic Stellate Cells: Implications in the Development and Progression of Type 2 Diabetes Mellitus.................................................. 73 Seung-Hyun Ko, Yu-Bai Ahn, Ki-Ho Song, and Kun-Ho Yoon 5 Renin-Angiotensin System Proteases and the Cardiometabolic Syndrome: Pathophysiological, Clinical and Therapeutic Implications.. 87 Guido Lastra, Camila Manrique, and James R. Sowers 6 The Role of the Renin-Angiotensin System in Hepatic Fibrosis........ 113 J.S. Lubel, F.J. Warner, and P.W. Angus 7 The Renin-Angiotensin System in the Breast ........................ 135 Gavin P. Vinson, Stewart Barker, John R. Puddefoot, and Massoumeh Tahmasebi v vi CONTENTS 8 Role of Local Renin-Angiotensin System in the Carotid Body and in Diseases ................................................... 155 Man Lung Fung and Po Sing Leung 9 Bone Homeostasis: An Emerging Role for the Renin-Angiotensin System.................................. 179 C. Sernia, H. Huang, K. Nguyuen, Y-H. Li, S. Hsu, M. Chen, N. Yu, and M. Forwood 10 The Renin-Angiotensin System and its Inhibitors in Human Cancers... 197 Lucienne Juillerat-Jeanneret 11 The Skeletal Muscle RAS in Health and Disease..................... 221 David R. Woods 12 Local Angiotensin Generation and AT Receptor Activation.......... 247 2 Joep H.M. van Esch and A.H. Jan Danser 13 ADAMs as Mediators of Angiotensin II Actions..................... 273 A.M. Bourne and W.G. Thomas Index................................................................ 303 PREFACE Thecirculatingrenin-angiotensinsystem(RAS)isahormonalsystemthatregulates blood pressure, electrolyte and fluid homeostasis. Angiotensin II (Ang II), along withbioactivepeptidessuchasAngIII,AngIVandAng(1-7)arethemaineffector peptides of the RAS. These peptides are the products of the proteolytic actions of renin, angiotensin-converting enzyme (ACE), ACE-2, and other angiotensin- processingpeptidases.Suchangiotensinpeptidesexerttheirfunctionsthroughtheir respective angiotensin receptors, namely AT1, AT2, AT4 and AT7 receptors. In the past decade, it has been recognized that numerous tissues and organs expresstheirownRAScomponentsandpeptideactivities.Suchintrinsicsystemsare particularlysuitedforprovidingautocrine,paracrineorintracrinepathwayshaving local functions that are different from, complementary to and, in some situations evencounteracting,thecirculatingRAS.Theselocalfunctionsinclude,butarenot limited to, cell growth, anti-proliferation, apoptosis, generation of reactive oxygen species, fibrogenesis, hormonal secretion, and vascular tone. The targets of these actionsextendbeyondtheestablishednervousandcardiovascularsystems,andnow reachsuchdiversetargetsasthebonetissue,carotidbody,adiposeandlivertissues, and the pancreas. Additionally, local RAS are subject to regulation by various physiologicalandpathophysiologicalconditions.BlockadeoftheRASthushasthe potentialtoprovideextensiveandnovelstrategiesforalternativeapproachesinthe treatment of cardiovascular, renal, hepatic, skeletal and pancreatic diseases. The significance and impact of the RAS in basic research and their clinical implications are reflected by the flourishing publication of original and review research articles; by the appearance of whole issues of journals dedicated to the RAS;andbyspecialistbooksontheRAS.Insucharapidlyevolvingenvironment, publicationsthatspanthespectrumfrombasicresearchtothebedside,fillapartic- ularly valuable niche for clinicians and researchers alike. Therefore, the major purpose of this seventh volume of Proteases in Biology and Disease series is to provideatopicalandtimelyforumforthecriticalappraisalofanareaofendocrine research that is expanding rapidly. In this book entitled “Frontiers in Research of the Renin-Angiotensin System on Human Disease”, a collection of 13 chapters from distinguished and world-class experts in the field has been presented on the contemporaryresearchoftheRASinhumandisease.Inthisrespect,itisclearthat vii viii PREFACE outstanding and stellar work on the novel roles of local RAS and their potential clinical application is being done.in laboratories and clinics across the globe. In Chapter 1, M.C. Chappell begins with “Role of ACE, ACE2 and Neprilysin in the Kidney”. In Chapter 2, D.J. Campbell continues with “ACE Inhibition in HeartFailureandIschaemicHeartDisease”.InChapter3,R.PezzilliandL.Fantini describe “Proteases of the Renin-Angiotensin System in Human Acute Pancre- atitis”. In Chapter 4, S.H. Ko et al. report on “The Renin-Angiotensin System in PancreaticStellateCells:ImplicationsintheDevelopmentandProgressionofType 2 Diabetes Mellitus”. In Chapter 5, G. Lastra et al. review the recent advances in “Renin-Angiotensin System Proteases and the Cardiometabolic Syndrome: Patho- physiological, Clinical and Therapeutic Implications”. In Chapter 6, J.S. Lubel et al. focus on “The Role of the Renin-Angiotensin System in Hepatic Fibrosis”. In Chapter 7, G.P. Vinson et al. discuss “The Renin-Angiotensin System in the Breast”. In Chapter 8, M.L. Fung and P.S. Leung contribute to “Role of Local Renin-Angiotensin System in the Carotid Body and in Diseases”. In Chapter 9, C. Sernia et al. concentrate on “Bone Homeostasis: an Emerging Role for the Renin-Angiotensin System”. In Chapter 10, L. Juillerat-Jeanneret discusses “The Renin-Angiotensin System and its Inhibitors in Human Cancers”. In Chapter 11, D.R. Woods deals with “The Skeletal Muscle RAS in Health and Disease”. In Chapter12,J.H.M.vanEschandA.H.JanDanserelaborateon“LocalAngiotensin Generation and AT2 Receptor Activation”. In the last Chapter 13, A.M. Bourne and W.G. Thomas end with “ADAMs as Mediators of Angiotensin II Actions” Finally, I would like to take this opportunity to express my sincere gratitude to ourSeriesEditors,UweLendeckelandNigelM.Hooper,forinvitingmetodosuch a great task for Springer: it has been a privilege. I also express my appreciation to my graduate student, Mr. Raymond K.K. Leung, for his skilled assistance on clerical work. This volume should be of general interest to the readership of our “Proteases in Biology and Disease” series, as well as being a comprehensive book for basic scientists, clinicians and newcomers to this field. Po Sing Leung Department of Physiology, Faculty of Medicine The Chinese University of Hong Kong, Hong Kong April 2007 CONTRIBUTORS Ahn,Yu-Bai DivisionofEndocrinology&Metabolism,DepartmentofInternal Medicine, The Catholic University of Korea, Seoul, Korea e-mail: [email protected] Angus, Peter W. Department of Gastroenterology and Hepatology, Austin Health, Studley Road, Heidelberg 3084, Melbourne, Victoria, Australia e-mail: [email protected] Barker, Stewart School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, United Kingdom e-mail: [email protected] Bourne, A.M. Molecular Endocrinology, Baker Heart Research Institute, PO Box 6492 St Kilda Road Central, Melbourne 8008, Victoria, Australia Department of Biochemistry and Molecular Biology, Monash University, Melbourne 3800, Australia e-mail: [email protected] Campbell, Duncan J. St. Vincent’s Institute of Medical Research and Department of Medicine, University of Melbourne, Fitzroy, Victoria, Australia e-mail: [email protected] Chappell, Mark C. Hypertension and Vascular Disease Center, Department of Physiology and Pharmacology, Molecular Medicine Programme, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1032, USA e-mail: [email protected] Chen, M. Department of Physiology & Pharmacology, School of Biomedical Science, University of Queensland, Brisbane, Australia e-mail: [email protected] ix x CONTRIBUTORS Danser, A.H. Jan Department of Pharmacology Room EE1418b Erasmus MC Dr. Molewaterplein 50 3015 GE Rotterdam, The Netherlands e-mail: [email protected] Fantini,L. DepartmentofInternalMedicineandGastroenterology,Sant’Orsola- Malpighi Hospital, Bologna, Italy e-mail: [email protected] Forwood, M. Department of Physiology & Pharmacology, School of Biomedical Science, University of Queensland, Brisbane, Australia e-mail: [email protected] Fung, Man Lung Department of Physiology, Faculty of Medicine Building, University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, The People’s Republic of China e-mail: [email protected] Hsu, S. Department of Physiology & Pharmacology, School of Biomedical Science, University of Queensland, Brisbane, Australia e-mail: [email protected] Huang, H. Department of Physiology & Pharmacology, School of Biomedical Science, University of Queensland, Brisbane, Australia e-mail: [email protected] Juillerat-Jeanneret, Lucienne University Institute of Pathology, Bugnon 25, CH1011 Lausanne, Switzerland e-mail: [email protected] Ko, Seung-Hyun Division of Endocrinology and Metabolism, Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea e-mail: [email protected] Lastra, Guido Department of Internal Medicine, University of Missouri- Columbia, Columbia, MO 65212, USA e-mail: [email protected] Leung,PoSing DepartmentofPhysiology,ChineseUniversityofHongKong, Shatin, Hong Kong e-mail: [email protected] Li, Y-H. Department of Physiology & Pharmacology, School of Biomedical Science, University of Queensland, Brisbane, Australia e-mail: [email protected] CONTRIBUTORS xi Lubel, J.S. Department of Gastroenterology, Austin Health, Studley Road, Heidelberg, Melbourne, Victoria, Australia e-mail: [email protected] Manrique, Camila Department of Internal Medicine, University of Missouri- Columbia, Columbia, MO65212, USA e-mail: [email protected] Nguyuen,K. DepartmentofPhysiology&Pharmacology,SchoolofBiomedical Science, University of Queensland, Brisbane, Australia e-mail: [email protected] Pezzilli, Raffaele Department of Internal Medicine and Gastroenterology, San’Orsola-Malpighi Hospital, Bologna, Italy e-mail: [email protected] Puddefoot,JohnR. SchoolofBiologicalandChemicalSciences,QueenMary University of London, Mile End Road, London E1 4NS, United Kingdom e-mail: [email protected] Sernia, Conrad Department of Physiology and Pharmacology, School of Biomedical Science, University of Queensland, Q4072, Brisbane, Australia e-mail: [email protected] Song,Ki-Ho DivisionofEndocrinology&Metabolism,DepartmentofInternal Medicine, The Catholic University of Korea, Seoul, Korea e-mail: [email protected] Sowers, James R. Department of Internal Medicine, University of Missouri- Columbia,Columbia,MO65212,USA e-mail: [email protected] Tahmasebi, Massoumeh School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, United Kingdom e-mail: [email protected] Thomas,WalterG. MolecularEndocrinology,BakerHeartResearchInstitute, PO Box 6492 St Kilda Road Central, Melbourne 8008, Victoria, Australia e-mail: [email protected] van Esch, Joep H.M. Department of Pharmacology, Erasmus MC, Rotterdam, The Netherlands e-mail: [email protected] xii CONTRIBUTORS Vinson, Gavin P. School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, United Kingdom e-mail: [email protected] Warner, F.J. A.W. Morrow Gastroenterology and Liver Centre, Centenary Institute of Cancer Medicine and Cell Biology, University of Sydney, Sydney, Australia e-mail: [email protected] Woods, David R. Department of Medicine, Royal Victoria Infirmary, Queen Victoria Road, Newcastle, NE1 4LP, U.K. e-mail: [email protected] Yoon, Kun-Ho Division of Endocrinology & Metabolism, Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea e-mail: [email protected] Yu, N. Department of Physiology & Pharmacology, School of Biomedical Science, University of Queensland, Brisbane, Australia e-mail: [email protected]