Table Of ContentVessel Wall in
Athero- and Thrombogenesis
Studies in the USSR
Edited by
E. I. Chazov and V. N. Smirnov
With Contributions by
s. s. v.
A. B. Alexeev A. Antonov G. Aptekar R. Berdichevsky
E. I. Chazov V. V. Dolgov L. V. Filatova E. N. Gerasimova
O. Ya. Kaufman A. N. Klimov V. A. Kosykh V. K. Kozlov
A. V. Krushinsky A. S. Kuznetsov V. L. Leyt in E. V. Ljubimova
R. A. Markosian A. V. Mazurov V. A. Metelskaya V. A. Nagornev
G. V. Nestaiko A. N. Orekhov N. V. Perova A. V. Pokrovsky
A. V. Popov O. M. Pozdnyakov S. N. Preobrazhensky
V. S. Repin V. N. Rosinova E. K. Ruuge I. A. Scherbakova
A. B. Shekhter V. N. Smirnov D. D. Sviridov V. P. Torchilin
V. A. Tverdislov A. M. Vikhert A. G. Vinogradov O. T. Zaikina
With 112 Figures
Springer-Verlag Berlin Heidelberg New York 1982
Professor Eugene I. Chazov
Director General of the USSR Research Center
for Cardiology of the USSR Academy of Medical Sciences
Petroverigsky Lane 10
Moscow 101837, USSR
Professor Vladimir N. Smirnov
Deputy Director General of the USSR Research Center
for Cardiology of the USSR Academy of Medical Sciences
Petroverigsky Lane 10
Moscow 101837, USSR
ISBN-13 :978-3-540-11384-3 e-ISBN-13 :978-3-642-68502-6
DOl: 10.1007/978-3-642-68502-6
Library of Congress Cataloging in Publication Data
Main entry under title:
Vessel wall in athero-and thrombogenesis.
Bibliography: p. I. Atherosclerosis-Etiology. 2. Thrombosis-Etiology. 3. Blood-vessels-Dis
eases-Research-Soviet Union. I. Chazov, E.I., II. Smirnov, V. N. (Vladimir Nikolaevich), 1937-
RC692.V44 616.1'36'071 82-814
ISBN-13:978-3-540-11384-3 (U. S.) AACR2
This work is subject to copyright. All rights are reserved, whether the whole or part of the material is con
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Contents
Introduction VII
Elements of Vessel Wall . . . . . . . . . . . . . . . . .
On the Endothelial Lining of Human Arteries at Genesis of the
Atherosclerotic Plaque. By A. M. Vikhert, V. N. Rosinova 3
Endothelial Injury and Polymorphism: A Quantitative Analysis by
Scanning Electron Microscopy. By V. S. Repin, V. V. Dolgov, O. T. Zaikina,
O. M. Pozdnyakov . . . . . . . . . . . . . . . . . . . . 13
Functional Characteristics of the Endothelium in the Dynamics of
Experimental Atherosclerosis Development. By V. A. Nagomev . 30
Morphological Analysis of Cells Isolated from the Intima and Media of
Human Aorta. By A. V. Krushinsky, A. N. Orekhov . . . . . . . 41
Functional and Metabolic Characterization of Cells from Normal
and Atherosclerotic Human Aorta. By A. N. Orekhov, V. A. Kosykh,
A. V. Pokrovsky . . . . . . . . . . . . . . . . . . . . . . 52
The Collagen-Elastic Framework of Major Arteries. By G. V. Nestaiko,
A. B. Shekhter . . . . . . . . . . . . . . . . . . . . . . . 63
Structural Changes of the Vascular Wall in Regional Hemodynamic
Disturbances. By O. Ya. Kaufman .............. 79
Complex Formation of Low Density Lipoproteins with Glycosaminoglycans
in the Arterial Wall. By A. S. Kuznetsov . . . . . . . . . . . . . . .. 91
Vessel Wall and Lipoproteins . . . . . . . . . . . . . . . 99
The Role of Apoproteins in Determination of Atherogeneity or
Antiatherogeneity of Blood Plasma Lipoproteins. By N. V. Perova,
I. A. Scherbakova, V. A. Metelskaya ........... . 101
Interaction of Lipoproteins and Apoproteins with Bilayer Lipid Membranes.
By V. A. Tverdislov, E. N. Gerasimova ................ 109
VI Contents
Features of Composition and Structure of High Density Lipoproteins at
Disulphatlipoproteinemias Accordingto Spin Label Electron Paramagnetic
Resonance Spectroscopy Data. By E. N. Gerasimova, E. K. Ruuge,
N. V. Perova .......................... 118
Mechanism of Lipoprotein Uptake into the Arterial Wall. By A. N. Klimov,
V. A. Nagomev ......................... 127
Interaction of Lipoproteins with Foam Cells. By A. V. Popov,
A. G. Vinogradov ................. . 134
A Biochemical and Morphological Study of Arterial Wall and Blood Plasma
Lipids in Human Atherosclerosis. By S. G. Aptekar, A. M. Vikhert 141
Interaction ofFluorescently-Labeled Low Density Lipoproteins with Human
Aortic Cells in the Primary Culture. By S. N. Preobrazhensky, A. S. Antonov,
V. A. Kosykh ....................... 151
Demonstration and Features of Low Density Lipoprotein Binding to
Platelets. By A. V. Mazurov, S. N. Preobrazhensky ....... 161
Vessel Wall and Platelets 171
A Model for Studying Platelet Interaction with Cellular and Macromolecular
Constituents of the Vessel Wall In Vitro. ByV. L. Ley tin, D. D. Sviridov 173
Targeted Liposome Transport to the Reconstituted Vessel Wall.
By V. N. Smimov, V. R. Berdichevsky, A. B. Alexeev, D. D. Sviridov,
V. P. Torchilin . . . . . . . . . . . . . . . . . . . . . . . 195
Adhesive and Thrombogenic Properties of Human Vascular Wall Cells in
Culture. By E. V. Ljubimova, A. N. Orekhov, V. L. Leyt in ...... 202
Platelet Shape Regulation. By R. A. Markosian, V. K. Kozlov, L. V. Filatova 211
Advances and Perspectives of Thrombo- and Atherogenesis Studies in the USSR.
By E. I. Chazov . . . . . . . . . . . . . . . . . . . . . . . . .. 216
Introduction
Mankind in the second half of the twentieth century has encountered a number of
social and economic problems, which, as never before, determine its future. Among
the main problems facing medicine, meriting distinction is organization of the
struggle against the increase of cardiovascular and oncological diseases which, with
the birthrate, are the main demographic indices of our planet.
According to the World Health-Organization, the deathrate from diseases of the
cardiovascular system has risen by 60% in recent years, and there has been a sharp
increase of myocardial infarctions and cases of sudden death in young people aged
25-30. The "geography" of heart and blood vessel diseases has changed: a dramatic
increase of morbidity has been recorded in rural regions, and in districts where
10-20 years ago the native population was practically unaffected by atherosclerosis.
Diseases of the cardiovascular system have become widespread among women as
well as men.
Cardiovascular diseases tax the national economy: they are responsible for over
half the mortality among people at the prime of their productive life. More than
50% of temporary disability is also accounted for by ischemic heart disease,
hypertension, stroke, etc.
It is known that the main clinical manifestations of cardiovascular diseases are
conditioned by atherosclerotic damage to vessels, and thus the approach to the
problem of atherosclerosis is primarily through the study of basic mechanisms of
plaque development, i. e., the analysis of pathologic processes at the molecular and
cellular levels. A new round of investigation has arisen as a result of intensive in
vasion of this field by cytologists, biochemists, and immunologists, equipped with
the modem methods of molecular and cell biology, immunochemistry, and
cytophysiology.
A sharp change in experimental technology and ideology has taken place in this
traditional field of medicine, and completely new fields of research have emerged. A
powerful arsenal of highly sensitive physical and chemical methods for study of cells
in culture has appeared as an aid to classical morphological methods of tissue and
organ analysis in situ.
Methods of cell biology have provided simple cell models for experiment and
opened the possibility of consecutive reconstitution of vessel wall elements and sur
face in culture. An unprecedented potential has materialized for studying the
physiology, proliferation, and cell-cell interaction of vessel endothelial and smooth
muscle cells in culture. Modem methods of electron microscopy, immunomorpholo
gy, and flow cytofluorometry reveal the fine details of normal and pathologic cell
ultrastructure. The paramount merit of the cell culture method is that it allows ex-
VIII Introduction
perimental study of human cells, i. e., it avoids the necessity of mimicking athero
sclerosis in animals.
Basic investigations in the field of cell biology have been directed at deciphering
the very fine alterations, metabolic shifts, and composition changes of vessel wall
cells at the early stages of atherosclerosis, when morphologic methods are incapable
of detecting changes. Crude morphologic wall changes are the result of the molecu
lar processes determining the vessel damage specificity in atherosclerosis. The main
efforts of specialists in this field have been directed at solving the following prob
lems:
1. The mechanism regulating cell and chemical homeostasis
2. Molecular mechanisms of endothelial injury and its repair
3. Mechanisms of intima hyperplasia
4. Lipidogenic and thrombogenic mechanisms of plaque formation
5. Origin of foam cells and pathways of extracellular matrix formation in the plaque
It is commonly accepted that these processes lead to the formation of an
atherosclerotic plaque. However, a unified, generally accepted concept explaining
the origin and consecutive mechanisms of plaque formation does not yet exist.
This book presents some results from the study of molecular and cellular aspects
of atherosclerosis carried out recently in several leading Soviet laboratories, but it
does not claim to be a comprehensive approach or reflection of the problem. Natu
rally, a number of published works have not been included here; the interested
reader can easily find the required material in the current literature. Atherosclerosis
is one of the most impetuously developing fields of experimental medicine and
pathology, and thus books of this type are only "dispatches" from the front line of
research. Their goal is to evaluate the most important trends and most promising
breakthroughs in experimental studies of atherosclerosis both in our country and
abroad.
E. I. Chazov V. N. Smirnov
Elements of Vessel Wall
On the Endothelial Lining of Human Arteries at
Genesis of the Atherosclerotic Plaque
A. M. Vikhert, V. N. Rosinova
USSR Research Center of Cardiology, Academy of Medical Sciences, Moscow, USSR
In recent years the study of local changes in the vascular wall at atherosclerosis has
become one of the leading approaches in investigations of the etiology and patho
genesis of atherosclerosis. Several authors have reported primary changes in the
vascular wall itself, encountered as early as childhood and youth, which can be con
sidered as the initial pre-lipid stages of atherosclerosis [1-3].
Limited focal intimal edema, along with other indications, was assigned to these
stages. The main manifestation of such injury is the focal accumulation in the artery
intima of a serous or serous-fibrin exudate as a result of increased penetrability of
the endothelium by blood plasma proteins [3-5]. Studies of early atherosclerotic
lesions have contributed to the recognition that along with the lipidogenic pathway
of atherosclerotic plaque development, other, nonlipidogenic pathways are possible,
the triggering mechanisms of which are still unclear. Some researchers assume that
local disruption of endothelial integrity or of its penetrability enhances the initial or
accelerating processes of atherogenesis [6, 7]. It is known that the endothelium
is a barrier between the blood and the vascular wall connective elements. The
study of endothelial physiology in tissue culture, using autoradiographic and elec
tron microscopy methods, has shown the polyfunctional nature of these cells and
their possible connection with the formation of atherosclerotic plaque [8-10]. The
selective transport and metabolism of matter through the endothelial barrier
noted by some authors is especially important in connection with atherogenesis
[11, 12]. The factors inducing endothelial injury lead to an increase of its perme
ability. These factors can be mechanical injury, hypertension, hypoxia, antigen-anti
body complexes, toxins, age, or the amount and quality of blood lipids [13, 14].
The possible consequence of endothelial injury is development of atheroscle
rotic plaque. An explanation of the mechanism of this process has been given by
Ross and collaborators [15-17], who proposed and proved by experiment the "re
action to injury" hypothesis. This states that there is massive accumulation of
platelets at sites of endothelial damage, which are then destroyed with the release of
the "platelet-derived growth factor", inducing the proliferation of arterial smooth
muscle cells and their consequent fatty degeneration and formation of the athero
sclerotic plaque.
Studies of the endothelium of humans with atherosclerosis are scarce. There are
only separate mentions, mainly touching upon its changes under scanning electron
microscopy [18]. The morphology of endothelial cells has been studied pre
dominantly in regeneration and inflammation of the vascular wall in animals [19],
and in experimentally induced atherosclerosis [20-23].
4 AM. Vikhert, V. N. Rosinova
Fig. la-c. Endothelia of the unaltered intima: a represented in the right coronary artery as
elongated cells with a clear cytoplasm and oval nucleus (male, age 33), X 700; b in the shoul
der artery the endothelial cells have a polygonal form and an eccentrically located nucleus with
a rounded or oval form (male, age 22), x 265; c elongated endothelial cells predominate in
aorta of a IS-year old girl, x 265
