Table Of ContentJean-Pierre Camilleri· Colin L. Berry
Jean-Noel Fiessinger . Jean Bariety (Eds.)
DISEASES
of the
ARTERIAL WALL
With 333 Figures
Springer-Verlag
London Berlin Heidelberg New York
Paris Tokyo
Jean-Pierre Camilleri
Professeur, Service d'Anatomie Pathologique et Unite de Recherche sur la Pathologie
Renale et Vasculaire, INSERM U28, Paris, France
Colin L. Berry
Professor, Department of Morbid Anatomy, Institute of Pathology, The London Hospital,
Whitechapel, London El lBB, UK
Jean-Noel Fiessinger
Professeur, Service de Medecine Interne et de Pathologie Vasculaire, Hopital Broussais,
Paris, France
Jean Bariety
Professeur, Service de Nephrologie et Unite de Recherche sur la Pathologie Renale et
Vasculaire, INSERM U28, Hopital Broussais, Paris, France
ISBN-13:978-1-4471-1466-6 e-ISBN-13:978-1-4471-1464-2
DOl: 10.1007/978-1-4471-1464-2
British Library Cataloguing in Publication Data
Diseases of the arterial wall.
I. Man. Arteries. Walls. Diseases I. Camilleri, Jean-Pierre. 1936- 616.1'3
ISBN-13:978-1-4471-1466-6
Library of Congress Cataloging-in-Publication Data
Diseases of the arterial wall/Jean-Pierre Camilleri ... let al.] (eds.).
p. cm.
Translated from the French.
Includes bibliographies and indpv
ISBN-13:978-1-4471-1466-6
I. Arteriosclerosis. 2. Arteries-Diseases. 3. Arteries-Pathophysiology. I. Camilleri, Jean-Pierre, 1936-
[DNLM: I. Arteries. 2. Vascular Diseases. WG 510 D611]
RC692.D56 1988
616.1'36--dcl9
DNLM/DLC
for Library of Congress 88-24887
CIP
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permitted under the provisions of the German Copyright Law of September 9, 1965, in its version of June 24,
1985, and a copyright fee must always be paid. Violations fall under the prosecution act of the German Copyright
Law.
Originally published in 1987 as Les Maladies de la Paroi Arterielle by Flammarion, 4 Rue Casimir-Delavigne,
75006 Paris
French Edition © Flammarion 1987
English Translation © Springer-Verlag Berlin Heidelberg 1989
Softcover reprint of the hardcover I st edition 1989
The use of registered names, trademarks etc. in this publication does not imply, even in the absence of a specific
statement, that such names are exempt from the relevant laws and regulations and therefore free for general use.
Product Liability: The publisher can give no guarantee for information about drug dosage and application thereof
contained in this book. In every individual case the respective user must check its accuracy by consulting other
pharmaceutical literature.
2128/3196/543210 (printed on acid-free paper)
Preface to the French Edition
La pathologie vasculaire a ete tres marquee par les progres biologiques de ces vingt demieres
annees. Le systeme arteriel est main tenant considere comme un organe a part entiere.
Modelee au cours de l'organogenese par les facteurs hemodynamiques, Ie paroi arterielle
maintient une structure hautement organisee et des proprietes mecaniques qui dependent
directement des conditions de pression et de debit. La monocouche endotheliale developpe
une surface de plusieurs centaines de m2 a l'interface sang-tissu; elle est a la fois un organe
endocrine complexe synthetisant de nombreuses proteines qui participent a l'hemostase,
une surface thromboresistante et hemocompatible, une barriere de permeabilite contr6lant
les echanges sang-tissus. Les cellules musculaires lisses constituent un tissu multifonctionnel,
contractile, assurant la synthese des composants structuraux responsables des proprietes
mecaniques de la paroi arterielle, la transmission de la force contractile, et une etonnante
activite reparatrice en reponse aux agressions. Tout ceci est soumis a un ensemble complexe
de communications cellulaires qui font de l'endothelium un veritable systeme recepteur
pour la paroi vasculaire.
Parallelement, ou a la suite de ces progres, l'angeiologie s'est progressivement affirmee
comme une specialite clinique. Debordant Ie cadre de la chirurgie vasculaire, elle integre
les concepts physiopathologiques au diagnostic et au traitement des maladies arterielles.
De cet effort d'integration est ne cet ouvrage, cherchant a concilier les connaissances
fondamentales es plus recentes et la demarche clinique. L'objectif est de reunir J'ensemble
des connaissances recemment acquises sur la physiologie et Ie physiopathologie de la
paroi arterielle, dans la me sure ou elles interviennent dans la definition d'une strategic
diagnostique et therapeutique. Les acrosyndromes ne sont pas individualises, ceci pour
eviter qu'a travers la pathologie de la microcirculation cer ouvrage n'englobe l'ensemble
des maladies systemiques: ils sont abordes au chapitre consacre aux vascularites. La plupart
des maladies arterielles sont en revanche envisagees. L'atherosclerose est consideree comme
modele de pathologie des communications cellulaires avec les particularites epidemio
logiques, hemodynamiques, pharmacologiques propres a chacune de ses localisations.
L'angiopathie diabetique est envisagee a part du fait des interrelations complexes entre les
perturbations biologiques et la micro-angiopathie. Les arteriopathies inflammatoires,
malgre les incertitudes pathogeniques qui subsistent, sont abordees du point de vue anato
moclinique. Ceci permet d'individualiser largement l'atteinte des grosses aI-teres (maladie
de Horton, Buerger, Takaysau) du cadre plus vaste des vascularites. Les maladies here
ditaires du tissu conjonctig ont frequemment une expression vasculaire: elles sont traitees
dans un souci exhaustif mais aussi pragmatique dans les criteres diagnostiques. Les aspects
anatomocliniques des dysplasies fibromusculaires, des anevrysmes, de l'hypertension arter
ielle, de la pathologie traumatique et peri-opertoire des arteres, des angiodysplasies et des
tumeurs vasculaires sont envisages dans les autres chapitres. Dans chacun de ces domaines,
l'analyse des relations structure-fonction nous parait essentielle pour comprendre les pheno
menes.pathologiques et pour etablir la strategie diagnostique et therapeutique.
vi Preface to the French Edition
En concretisant notre projet nous avons pris conscience du risque de desequilibre entre
une biologie en progres incessant et une demarche clinique pragmatique et parfois empirique
souvent envisagee de far;on trop fragmentaire. Nous souhaitons que l'ambition du projet
et son originalite nous permettent de beneficier de l'indulgence de nos lecteurs. D'ores et
deja, nous remercions vivement tous les auteurs francophones et anglophones qui, en
acceptant de participer a la redaction, ont pris Ie pari de l'angeiologie.
Jean-Pierre Camilleri
Colin L. Berry
Jean-Noel Fiessinger
Jean Bariety
REMERC lEMENTS
A tous ceux et toutes celles qui ont contribue, par leur competence, a la realisation de
cet ouvrage.
Nous remercions tout particulierement Maurice Wolfelsperger qui a realise la majeure
partie de l'iconographie et nous a aides a sa mise en pages, de meme que Sylviane Robin
et Brigitte Jarrin qui ont assure avec devouement et competence les taches de secretariat.
Preface to the English Edition
The emphasis on the development of understanding of the arterial tree as an organ system,
its modelling by physical forces, the complexity of interactions among its components and
the specialist properties of the component cells and their products are emphasized in the
Preface to the French edition of this book. These factors and the progress made in clinical
diagnostic techniques have allowed progressively better evaluation of structure/function
relationships in the system, and assessment of their disturbance in disease.
For these reasons this volume was conceived as a text helpful to those who work at the
clinical/laboratory interface so essential for the proper management of vascular disease.
The large segment of the population affected by these diseases requires considered care
based on a thorough knowledge of the background of the natural history of the various
processes affecting the wall and of the way in which investigation is organized.
The generosity of non-English-speaking colleagues in permitting changes in their trans
lated texts has been unstinting. It is hoped that the English text has not altered expressions
of view significantly; we have tried only to facilitate expression of the authors' meaning.
London
February 1989 Colin Berry
Contents
I CELLULAR AND MOLECULAR BIOLOGY OF THE NORMAL ARTERIAL WALL
1 Endothelial and Smooth-Muscle Cells
/. Huttner, O. Kocher and G. Gabbiani. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Structure of the Normal Arterial Wall. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
The Endothelial Cell .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Biological Behaviour and Morphology of Endothelial Cells. . . . . . . . . . . . . . . . . 4
Functional Properties of Vascular Endothelium. . . . . . . . . . . . . . . . . . . . . . . . . . . 10
The Smooth-Muscle Cell ................................................ 15
Biological Behaviour of Smooth-Muscle Cells ............................ 15
Functional Morphology of Vascular Smooth Muscle. . . . . . . . . . . . . . . . . . . . . . 18
Interactions Between Endothelial and Smooth-Muscle Cells .................. 28
Communication Between Endothelial and Smooth-Muscle Cells Mediated Via
Humoral Mechanisms .............................................. 28
Communication Between Endothelial and Smooth-Muscle Cells Mediated Via
Direct Cell-to-Cell Contacts ......................................... 29
References .......................................................... 30
2 Extracellular Matrix ofthe Arterial Vessel Wall
L. Robert and P. Birembaut . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
Collagens ............................................................. 43
Biochemistry ........................................................ 43
Morphology ........................................................ 45
Elastin ............................................................... 46
Biochemistry ........................................................ 46
Morphology ........................................................ 48
Proteoglycans ......................................................... 49
Biochemistry ........................................................ 49
Morphology ........................................................ 50
Structural Glycoproteins ................................................ 50
Biochemistry ........................................................ 50
Morphology ........................................................ 52
General Arrangement of Extracellular Matrix of the Vascular Wall. . . . . . . . . . . . 52
References ............................................................ 53
x Contents
3 Organogenesis of the Arterial Wall
C. L. Berry ............................................................ 55
Structural Organization of Vessel Walls ................................... 56
Early Development of the Circulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
Structural Organization of the Arterial Wall. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
Static Mechanics ..................................................... 60
Scleroproteins in the Aortic Wall. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
Developmental Implications ........................................... 63
Arterial Wall Nutrition ................................................. 66
Exceptional Areas in Vascular Development ............................... 66
Ductus Arteriosus .................................................... 66
Coarctation ......................................................... 67
Coronary Vessels and Vascular Cushions ................................ 68
Conclusions ........................................................... 68
References ............................................................ 68
4 Age-Related Morphological Changes of the Arterial Wall
H. Bouissou, M. T. Pieraggi and M. Julian.. . . ... ..... ... . . ... .... . ... . ... .. 71
"Elastic"-Type Arteries ................................................. 71
"Muscular"-Type Arteries. . . . . ... . . . ... . .... . .. . . . ... . ... ... . . ... . ... ... 75
Assessment of Ageing of the Arterial Wall. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
References ............................................................ 77
5 Effects of "Ageing" on Arterial Cells In Vitro
Monique Breton and J. Picard. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
Introduction .......................................................... 79
Cell Culture Techniques ................................................. 79
Smooth-Muscle Cells ................................................. 79
Endothelial Cells ..................................................... 80
Growth of Arterial Cells ................................................ 80
Smooth-Muscle Cells ................................................. 80
Endothelial Cells ..................................................... 81
Growth Factors and the Proliferation of Arterial Cells. . . . . . . . . . . . . . . . . . . . . 81
Metabolic Activities of Arterial Cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
Glycosaminoglycans and Proteoglycans ................................. 83
Fibrous Proteins: Collagen and Elastin .................................. 85
Low-Density Lipoproteins ............................................. 85
Conclusion ............................................................ 86
References ............................................................ 86
6 Structural Modifications of the Arterial Wall in Hypertension
J.-B. Michel, J. L. Salzmann and M. Safar. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
Introduction .......................................................... 91
Structural Modifications of the Arterial System as a Consequence of Hypertension 91
Structural Modifications of the Arterial Wall as a Result of High Blood Pressure 93
Complications: Lacunes and Atherosclerosis ............................. 93
Effect of Treatment ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
Similarity Between the Ageing Process and Hypertension in the Arterial Wall. . . 94
References ............................................................ 95
Contents xi
7 Adrenergic and Non-adrenergic Neural Control of the Arterial Wall
K. K. Dhital and G. Burnstock ........................................... . 97
Introduction 97
Structure of the Vascular Neuroeffector Junction ........................... . 97
Pattern of Perivascular Innervation ...................................... . 98
Development and Regeneration of Perivascular Innervation ................. . 99
Adrenergic Nerves .................................................. . 100
Cholinergic Nerves .................................................. . 100
Non-adrenergic, Non-cholinergic Nerves ................................. . 102
Purinergic Nerves ................................................... . 102
Aminergic Nerves ................................................... . 103
Peptidergic Nerves .................................................. . 105
Neuromodulation and Co-transmission ................................... . III
Concluding Comments ................................................. . 113
References ........................................................... . 114
8 The Arterial Wall and the Haemostatic Process
Y. J. Legrand and L. O. Drouet .......................................... . 127
Introduction ......................................................... . 127
Thromboresistance of the Endothelium ................................... . 128
Thromboresistance in Relation to Primary Haemostasis ................... . 128
Thromboresistance in Relation to Plasma Coagulation .................... . 129
Thromboresistance in Relation to Fibrinolysis ........................... . 129
The Thrombogenicity of the Subendothelium .............................. . 130
Ex Vivo Study of the Thrombogenicity of the Subendothelium ............. . 130
In Vitro Study of the Vascular Thrombogenic Macromolecules. ............ . 132
Structural Determinants of Collagen and Microfibrils Involved in the Throm-
bogenicity of Subendothelium ....................................... . 132
In Vivo Studies on the Thrombogenicity of Sub endothelium ............... . 135
Mechanism of Platelet Activation ........................................ . 135
Conclusion 138
References ........................................................... . 138
9 The Vascular Wall and Hormonal Control of Vasomotor Function
F. Alhenc-Gelas and P. Corvol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143
Vasoactive Peptide Metabolism of the Vascular Endothelium. . . . . . . . . . . . . . . . . 144
Converting Enzyme or Kininase II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
Does a Complete Renin-Angiotensin System Exist in the Vascular Endothelium? 149
Other Peptidases of the Vascular Endothelium. . . . . . . . . . . . . . . . . . . . . . . . . . . . 150
Modulation by the Endothelium of the Physiological and Pharmacological Activity
of Vasoactive Compounds. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150
Stimulation of Prostaglandin Formation by Vasoactive Agents in the Vascular
Endothelium ...................................................... 151
Vasomotor Reactions Depending on the Vascular Endothelium. . . . . . . . . . . . . 153
Physiological and Physiopathological Consequences of the Role of the Endo-
thelium in Controlling Vasomotor Activity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
Endocrine Function of the Smooth-Muscle Cell: The Renin-Secreting Cell. . . . . . 154
Morphology of Renin-Secreting Cells ................................... 154
Renin Structure and Renin Precursor Maturation. . . . . . . . . . . . . . . . . . . . . . . . . 155
Role of Renin Secretion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 156
Note Added in Proof. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
References ............................................................ 157
xii Contents
II PATHOPHYSIOLOGY OF EXPERIMENTAL AND HUMAN ATHEROSCLEROSIS
10 The Lesions of Atherosclerosis
C.L. Berry ........................................................... . 163
Early Changes, Fatty Streaks and Gellatinous Elevations .................. . 163
The Fibroatheromatous Plaque and Early Established Lesion .............. . 164
The Complicated Lesion ............................................. . 164
The Pathogenesis of the Lesions ......................................... . 164
The Role of Lipids .................................................... . 165
References ........................................................... . 166
11 Atherosclerosis: Cellular Aspects
o. Kocher, /. Huttner and G. Gabbiani .................................... . 167
Introduction ......................................................... . 167
Role of Endothelium ................................................... . 167
Modifications of the Endothelium in Pathological Conditions .............. . 168
Endothelial Dysfunction as a Predisposing Factor for the Development of Athero-
sclerosis ......................................................... . 171
Role of Smooth-Muscle Cells ........................................... . 172
The Arterial Smooth-Muscle Cell in Experimental Atherosclerosis .......... . 172
Arterial Smooth-Muscle Cells in Human Atherosclerosis .................. . 174
Growth Factors for Arterial Smooth-Muscle Cells ....................... . 176
Monoclonality of Atheromatous Smooth-Muscle Cells .................... . 177
The Role of the Macrophage ............................................ . 177
Conclusions .......................................................... . 178
References 179
12 Extracellular Matrix Changes in Atherosclerosis
T.N. Wight .......................................................... . 185
Collagens ............................................................ . 185
Proteoglycans ........................................................ . 187
Elastin .............................................................. . 190
Glycoproteins ........................................................ . 191
Summary ............................................................ . 192
References ........................................................... . 192
13 Lipid Accumulation in the Vessel Wall
S. Moore ............................................................ . 197
Introduction ......................................................... . 197
Lesions Induced by Injury .............................................. . 198
Injury from Indwelling Aortic Catheter ................................. . 198
Immunological Injury ............................................... . 198
Inhibition of Lesion Development ..................................... . 199
Balloon-Catheter Removal of the Endothelium .......................... . 200
Lipid Accumulation in Lesions .......................................... . 200
Lipid-Containing Lesions Following Vascular Injury in Man .............. . 200
Relationship of Injury to "Early" Human Atherosclerotic Lesions .......... . 201
Mechanisms of Lipid Accumulation in Injury-Induced Lesions ............. . 202
