Table Of ContentPlatelets, Thrombosis and the Vessel Wall
Advances in Vascular Biology
A series of books bringing together important advances and reviewing all areas
of vascular biology.
Edited by Mathew A.Vadas, The Hanson Centre for Cancer Research, Adelaide,
South Australia and John Harlan, Division of Hematology, University of
Washington, Seattle, USA.
Volume One
Vascular Control of Hemostasis
edited by Victor W.M.van Hinsbergh
Volume Two
Immune Functions of the Vessel Wall
edited by Göran K.Hansson and Peter Libby
Volume Three
The Selectins: Initiators of Leukocyte Endothelial Adhesion
edited by Dietmar Vestweber
Volume Four
The Role of Herpesviruses in Atherogenesis
edited by David P.Hajjar and Stephen M.Schwartz
Volume Five
Plasma Lipids and Their Role in Disease
edited by Philip J.Barter and Kerry-Anne Rye
Volume Six
Platelets, Thrombosis and the Vessel Wall
edited by Michael C.Berndt
Volume in Preparation
Structure and Function of Endothelial Cell to Cell Junctions
edited by Elisabetta Dejana
This book is part of a series. The publisher will accept continuation orders which may
be cancelled at any time and which provide for automatic billing and shipping of each
title in the series upon publication. Please write for details.
Platelets, Thrombosis and
the Vessel Wall
edited by
Michael C. Berndt
Baker Medical Research Institute
Prahran, Victoria
Australia
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British Library Cataloguing in Publication Data
Platelets, thrombosis and the vessel wall.—(Advances in
vascular biology; v. 6)
1. Blood platelets 2. Thrombosis 3. Hemostasis
I. Berndt, Michael C.
612.1′17
ISBN 0-203-30432-2 Master e-book ISBN
ISBN 0-203-35376-5 (Adobe eReader Format)
ISBN: 90-5702-369-5 (Print Edition)
ISSN: 1072–0618
CONTENTS
Series Preface vii
Preface viii
List of Contributors ix
Chapter 1 Thrombopoietin
John E.J.Rasko and C.Glenn Begley 1
Chapter 2 Platelets and Fibrinolysis
Jane A.Leopold and Joseph Loscalzo 29
Chapter 3 von Willebrand Factor and Platelet Adhesion
Christopher M.Ward and Michael C.Berndt 56
Chapter 4 A Unique Receptor for a Unique Function: The
Glycoprotein Ib-IX-V Complex in Platelet Adhesion and
Activation
José A.López, David R.Smith and Jing-Fei Dong 88
Chapter 5 The Platelet Glycoprotein IIb-IIIa Complex (Integrin α β )
IIb 3
Xiaoping Du 111
Chapter 6 The Platelet Cytoskeleton
Joan E.B.Fox and Sylvie C.Meyer 137
Chapter 7 The Role of the Phosphoinositide-Derived Second Messenger
Molecules in Platelet Activation
Janine K.Campbell, Susan Brown, Adam D.Munday and
Christina A.Mitchell 169
Chapter 8 The Biology of CD36
Rick F.Thorne, Douglas J.Dorahy, Robyn M.Wilkinson and
Gordon F.Burns 198
Chapter 9 CD9 Structure and Function
Lisa K.Jennings, Joseph T.Crossno, Jr. and Melanie M.White 230
Chapter 10 Neutrophil-Platelet Interactions
Dominique Pidard, Mustapha Si-Tahar and Michel Chignard 253
Chapter 11 P-Selectin
Rodger P.McEver 279
Chapter 12 Role of PECAM-1 in Vascular Biology
Robert K.Andrews and Michael C.Berndt 309
Chapter 13 Role of Thrombospondins in Vascular Biology
Philip J.Hogg and Kylie A.Hotchkiss 338
Chapter 14 Platelet-Derived Growth Factor: Regulation of Gene
Expression and Roles in Vascular Pathobiology
Levon M.Khachigian, Eric S.Silverman, Volkhard Lindner, Amy
J.Williams, Colin N.Chesterman and Tucker Collins 356
Chapter 15 Antiphospholipid Antibodies
Tracy McNally and Michael C.Berndt 384
Chapter 16 Resistance to Activated Protein C and Inherited
Thrombosis: Molecular Mechanism, Diagnosis and Clinical
Management
Ross Baker and John Eikelboom 410
Index 451
SERIES PREFACE
It is our privilege to live at a time when scientific discoveries are providing insights into
human biology at an unprecedented rate. It is also a time when the sheer quantity of
information tends to obscure underlying principles, and when hypotheses or insights that
simplify and unify may be relegated to the shadow of hard data.
The driving force for editing a series of books on Vascular Biology was to partially
redress this balance. In inviting editors of excellence and experience, it is our aim to draw
together important facts, in particular areas of vascular biology, and to allow the
generation of hypotheses and principles that unite an area and define newer horizons. We
also anticipate that, as is often the case in biology, the formulation and application of
these principles will interrelate with other disciplines.
Vascular biology is a frontier that has been recognised since at least the time of
Cohnheim and Metchikoff, but has really come into prominence over the last 10–15
years, once the molecules that mediate the essential functions of the blood vessel started
to be defined. The boundaries of this discipline are, however, not clear. There are
intersections, for example, with hypertension and atherogenesis that bring in,
respectively, neuroendocrine control of vessel tone and lipid biochemistry which exist as
separate bodies of knowledge. Moreover, it would be surprising if some regional vascular
biology (for example, pulmonary, renal, etc.) were not to emerge as subgroups in the
future. Our aims for the moment, however, are to concentrate on areas of vascular
biology that have a wide impact.
It is our hope to publish two books each year for the next 3–4 years. Indeed the first
five books have been commissioned and address areas primarily in endothelial biology
(hemostasis and thrombosis), immunology, leukocyte adhesion molecules, platelet
adhesion molecules, adhesion molecules that mediate cell-cell contact. Subsequent
volumes will cover the physiology and pathology of other vascular cells as well as
developmental vascular biology.
We thank the editors and contributors for their very hard work.
Mathew VADAS John HARLAN
PREFACE
Unstable angina, myocardial infarction and stroke, precipitated by thrombosis, are the
leading combined causes of death in the Western world. In response to vascular trauma,
platelets rapidly adhere to the exposed subendothelial matrix. At high shear flow rates, as
would occur at sites of stenosis, the initial platelet adhesion is dependent upon von
Willebrand factor and a specific von Willebrand factor receptor on platelets, the GP Ib-
IX-V complex. Platelet activation through agonist and adhesion receptors leads to a
cascade of signaling events, cytoskeletal re-organization and secretion of the contents of
platelet dense bodies and alpha-granules. Substances released from platelets include ADP
that acts in the recruitment of additional platelets to the developing thrombus. A variety
of proteins involved in the regulation of coagulation and fibrinolysis are also released as
well as proteins such as thrombospondin and platelet-derived growth factor that are
involved in subsequent vascular remodeling and wound repair. Concomitant with platelet
activation and release, the platelet integrin, GP-IIb-IIIa, is converted from a low affinity
to a high affinity receptor for fibrinogen and von Willebrand factor leading to platelet
aggregation and subsequent thrombus. Activated platelets also express adhesion receptors
for neutrophils and endothelial cells and therefore there is the potential for cross-talk
between these cell types in the developing thrombus.
In recent years, there have been major advances in our understanding of platelets and
their role within the vasculature. The purpose of this text is not to provide an exhaustive
overview of this subject, but to highlight key aspects of platelet function in the regulation
of thrombosis and haemostasis. The various chapters cover the regulation of
megakaryocytopoiesis and platelet production, platelet cell surface receptors and ligands
involved in platelet adhesion, aggregation, and the interaction of platelets with leukocytes
and endothelial cells, the role of the platelet cytoskeleton in agonist-dependent platelet
activation, the role of platelets in regulation of fibrinolysis, and mechanisms of cross-talk
between platelets, leukocytes and endothelium. Finally, there are two chapters
highlighting two major clinical causes of thrombosis, circulating anti-phospholipid
antibodies and genetic predisposition.
LIST OF CONTRIBUTORS
Andrews, Robert K.
Hazel and Pip Appel Vascular Biology Laboratory
Baker Medical Research Institute
PO Box 348, Commercial Road
Prahran,VIC 3181
Australia
Baker, Ross
Clinical Thrombosis Unit
Haematology Department
Royal Perth Hospital
University of Western Australia
GPO Box X2213
Perth, WA 6001
Australia
Begley, C.Glenn
The Walter and Eliza Hall Institute for Medical Research
PO Royal Melbourne Hospital
Melbourne, VIC 3050
Australia
Berndt, Michael C.
Hazel and Pip Appel Vascular Biology Laboratory
Baker Medical Research Institute
PO Box 348, Commercial Road
Prahran,VIC 3181
Australia
Brown, Susan
Department of Medicine
Monash Medical School
Box Hill Hospital
Nelson Road
Box Hill, VIC 3128
Australia
Burns, Gordon F.
Cancer Research Unit, Level 5
