Advances in lipid research. Vol. 18, 1981

326 Pages·1981·29.324 MB·English

by  Rodolfo Paoletti, David Kritchevsky

EDITORIAL ADVISORY BOARD
B. LEWIS G. SCHLIERF
A. V. NICHOLS C. SlRTORI
G. H. ROTHBLAT R. W. WlSSLER
CONTRIBUTORS TO THIS VOLUME
AKHLAQ A. FAROOQUI LINDA A. SCHULER
KATTI FISCHER-DZOGA JON A. STORY
WERNER FORSTER JEROME F. STRAUSS III
PETER HOFFMANN TOSHINOBU TANAKA
TATU A. MIETTINEN A. G. VERESHCHAGIN
MlNDY F. ROSENBLUM DRAGOSLAVA VESSELINOVITCH
A. V. ZHUKOV
EDITORIAL ADVISORY BOARD
B. LEWIS G. SCHLIERF
A. V. NICHOLS C. SlRTORI
G. H. ROTHBLAT R. W. WlSSLER
CONTRIBUTORS TO THIS VOLUME
AKHLAQ A. FAROOQUI LINDA A. SCHULER
KATTI FISCHER-DZOGA JON A. STORY
WERNER FORSTER JEROME F. STRAUSS III
PETER HOFFMANN TOSHINOBU TANAKA
TATU A. MIETTINEN A. G. VERESHCHAGIN
MlNDY F. ROSENBLUM DRAGOSLAVA VESSELINOVITCH
A. V. ZHUKOV
Advances
in
Lipid
Research
Volume 18
Edited by
Rodolfo Paoletti
Institute of Pharmacology
Milan, Italy
David Kritchevsky
The Wistar Institute
Philadelphia, Pennsylvania
1981
ACADEMIC PRESS
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ISBN 0-12-024918-9
PRINTED IN THE UNITED STATES OF AMERICA
81 82 83 84 9 8 7 6 5 4 3 2 1
LIST OF CONTRIBUTORS
Numbers in parentheses indicate the pages on which the authors' contributions begin.
AKHLAQ A. FAROOQUI,* Department of Biochemistry, University of
Georgia, Athens, Georgia 30602 (159)
KATTI FISCHER-DZOGA, Department of Pathology and the Specialized
Center of Research in Atherosclerosis, The University of Chicago,
Chicago, Illinois 60637 (1)
WERNER FORSTER, Department of Pharmacology and Toxicology, Martin
Luther University Halle-Wittenberg, 402 Halle/Saale, German Demo­
cratic Republic (203)
PETER HOFFMANN, Department of Pharmacology and Toxicology, Martin
Luther University Halle-Wittenberg, 402 Halle/Saale, German Demo­
cratic Republic (203)
TATU A. MIETTINEN, Second Department of Medicine, University of
Helsinki, 00290 Helsinki 29, Finland (65)
MINDY F. ROSENBLUM, Departments of Obstetrics and Gynecology and
Physiology, University of Pennsylvania School of Medicine, Philadel­
phia, Pennsylvania 19104 (99)
LINDA A. SCHULER, Departments of Obstetrics and Gynecology and
Physiology, University of Pennsylvania School of Medicine, Philadel­
phia, Pennsylvania 19104 (99)
JON A. STORY, Department of Foods and Nutrition, Purdue University,
West Lafayette, Indiana 47907 (229)
JEROME F. STRAUSS III, Departments of Obstetrics and Gynecology and
Physiology, University of Pennsylvania School of Medicine, Philadel­
phia, Pennsylvania 19104 (99)
* Present address: Department of Parasitology, College of Veterinary Medicine, University
of Georgia, Athens, Georgia 30602.
ix
X LIST OF CONTRIBUTORS
TOSHINOBU TANAKA, Departments of Obstetrics and Gynecology and
Physiology, University of Pennsylvania School of Medicine, Philadel­
phia, Pennsylvania 19104 (99)
A. G. VERESHCHAGIN, Lipid Biochemistry Research Unit, Institute of Plant
Physiology, Academy of Sciences, Moscow, USSR (247)
DRAGOSLAVA VESSELINOVITCH, Department of Pathology and the Special­
ized Center of Research in Atherosclerosis, The University of Chicago,
Chicago, Illinois 60637 (1)
A. V. ZHUKOV, Lipid Biochemistry Research Unit, Institute of Plant
Physiology, Academy of Sciences, Moscow, USSR (247)
PREFACE
The study of atherosclerosis encompasses many scientific disciplines but
because of the identification of elevated serum cholesterol levels as a risk
factor there is an extremely strong connection between the areas of
atherosclerosis and lipid research. The subject of atherosclerosis has been
discussed in two earlier volumes of this series. With the expansion of in­
terest into different areas involving lipid metabolism (e.g., tissue culture)
the Editors felt that a discussion of atherosclerosis would again be ap­
propriate. Techniques in atherosclerosis research are the subject of the first
chapter in this volume. The second chapter deals with the influence of
lipid-lowering drugs on bile acid metabolism. Cholesterol metabolism
should be thought of in terms of its precursors and metabolic products as
well as the sterol itself. Since bile acid metabolism exerts an influence on
cholesterol metabolism this chapter will be of interest to all investigators in
the fields of lipid and drug metabolism. Cholesterol is known to be the
precursor of adrenocortical and sex hormones, being converted to the ap­
propriate hormone in the appropriate tissue. Cholesterol metabolism in
these specialized tissues involves a number of metabolic steps including up­
take, esterification or hydrolysis, and side chain cleavage. The third con­
tribution to this volume is a detailed discussion of cholesterol metabolism
in ovarian tissue.
Sulfolipids represent a unique family of compounds whose principal role
appears to be as a constituent of membranes or other biological structural
units. This subject has not been addressed since the first volume of this
series. Chapter 4 brings the field up-to-date.
Polyunsaturated fatty acids have long been known to affect serum and
plasma lipid levels. It has recently become evident that they may also affect
other biological parameters such as blood pressure. The fifth chapter
reviews one special area of the influence of dietary linoleic acids on blood
pressure regulation in rats.
The sixth chapter in this volume reviews a relatively recent popular
dietary phenomenon—the influence of nonnutritive fiber. In this chapter
the effects of dietary fiber on lipid metabolism are reviewed. The influence
xi
xii PREFACE
of fiber on lipid-associated diseases is also discussed. The more avid pro­
ponents of the use of dietary fiber have presented exhaustive lists of condi­
tions which are either due to its lack or can be cured by its addition to the
diet. This chapter helps to put the field into proper perspective.
With the proliferation of analytical methods it is possible now to identify
a large variety of interesting biological materials. Do our methods of sam­
ple preparation match the modalities for their measurement? The last
chapter of this book presents a thorough review of techniques for analysis
of polar lipids. This chapter is of importance to any worker in the field of
natural products and especially so for those whose interests are in lipid
chemistry.
RODOLFO PAOLETTI
DAVID KRITCHEVSKY
ADVANCES IN LIPID RESEARCH, VOL. 18
Techniques in Pathology in Atherosclerosis Research1
DRAGOSLAVA VESSELINOVITCH AND KATTI FISCHER-DZOGA
Department of Pathology and the
Specialized Center of Research in Atherosclerosis
The University of Chicago
Chicago, Illinois
1
I. Introduction
II. Methods of Induction of Atherosclerosis 4
A. Nutritional Factors 6
B. Physical Methods 8
C. Chemical Injury 12
D. Immunological Injury 13
III. Diagnosis of Atherosclerosis and Assessment of Lesions 16
A. Clinical Diagnosis 16
B. Gross Evaluation of Lesions 19
C. Microscopic Evaluation 24
D. Immunochemical Techniques 40
IV. Epidemiology 41
V. Tissue Culture • 44
VL Statistical Evaluation of Morphometric Results 47
VII. Summary 48
References 49
I. Introduction
The problems involved in the study of atherosclerosis are by no means
simple. The multifactorial pathogenesis and the intrinsic and extrinsic com­
plexity of this disease make its study difficult and its problems quite
unique, not comparable to the study of infectious diseases or a deficiency
state.
In the latter part of this century there has been an increased emphasis on
the study of this disease in humans, as well as considerable interest in ex­
perimental atherosclerosis, and both of these approaches have yielded
much valuable knowledge. We realize now that the intrinsic complexity of
this disease is far greater than the lesion suggests. While there is a great
1
The studies conducted in this laboratory and referred to in this article were supported in
part by funds from USPHS Grants HL-15062 and The University of Chicago's Louis Block
Fund for Basic Research and Advanced Study.
1
Copyright © 1981 by Academic Press, Inc.
All rights of reproduction in any form reserved.
ISBN 0-12-024918-9
2 DRAGOSLAVA VESSELINOVITCH AND KATTI FISCHER-DZOGA
variety of atherogenic agents, it appears that the response potential of the
arterial wall is quite limited and nonspecific. Therefore, the lesions
resulting from widely different types of injuries are often similar and in
some cases indistinguishable. Consequently, the study of atherosclerosis is
best divided into two parts: (1) the assessment of causative agents, and (2)
the assessment of resulting damage at various levels. The former would
have to take into consideration the differential atherogenic power of
various causative factors—e.g., stimulators, accelerators, or contributors,
while the latter includes the study of blood elements and the artery wall,
both grossly and at the cellular level. Finally, the crucial relationship be­
tween these two aspects must be evaluated.
Accurate diagnosis of atherosclerosis in living subjects and precise
evaluation of the duration, degree, and severity of the disease prior to the
clinical symptoms are still not possible. The clinical manifestations of le­
sions and their consequences are extremely variable, being dependent on
the location and the character of the lesions, the extent to which they cause
occlusion or dilatation of the vessel, and of course on the functional
capacity of their collaterals.
All these considerations necessitate approaches of assessing and grading
the disease which involve a variety of methods and techniques. Research
must include both retrospective and prospective studies combining observa­
tional and clinical work with well-controlled experimental studies, taking
into account both qualitative and quantitative aspects. New approaches,
developed on the basis of progress made in biochemistry and cellular and
molecular biology in the last few years, will help us to obtain more accurate
results in the investigation of atherosclerosis and to come closer to an inter­
pretation and understanding of the mechanisms behind it. The infiltration
of new approaches into the investigation of this disease should have a pro­
found influence on the character and dimension of these studies, not in any
way diminishing the value of previous work, but rather extending it in
many ways.
Epidemiological studies in human patients were employed relatively early
in the history of atherosclerotic research. At first, they were casual and
limited to small numbers of observations, but eventually they evolved into
highly critical and systematic studies, especially in the case of prospective
epidemiological work. Such studies investigate either various risk factors or
different hypocholesterolemic agents. Although in most of these studies
age, sex, and race can be matched, the control of many other variables
associated with differences in economic or social conditions, intellectual
levels, and personal habits cannot be well controlled in human subjects.
Furthermore, despite considerable improvement during recent years, ac­
curate and easy measurements of the extent and severity of lesions in vivo