Table Of ContentFRONTIERS 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]
