Drugs Affecting Lipid Metabolism VIII

502 Pages·1985·15.18 MB·English

by  Robert W. Wissler (auth.)

DRUGS AFFECTING
LIPID METABOLISM VIII
ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY
Editorial Board:
NATHAN BACK, State University of New York at Buffalo
NICHOLAS R. DI LUZIO, Tulane University School of Medicine
EPHRAIM KATCHALSKI-KATZIR, The Weizmann Institute of Science
DAVID KRITCHEVSKY, Wistar Institute
ABEL LAJTHA, Rockland Research Institute
RODOLFO PAOLETTI, University of Milan
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DRUGS AFFECTING LIPID METABOLISM VIII
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DRUGS AFFECTING
LIPID METABOLISM VIII
Edited by
David Kritchevsky
The Wistar Institute of Anatomy and Biology
Philadelphia, Pennsylvania
William L. Holmes
West Chester, Pennsylvania
and
Rodolfo Paoletti
Institute of Pharmacology and Pharmacognosy
University of Milan
Milan, italy
PLENUM PRESS • NEW YORK AND LONDON
Library of Congress Cataloging in Publication Data
International Symposium on Drugs Affecting Lipid Metabolism (8th: 1983:
Philadelphia, Pa.
Drugs affecting lipid metabolism VIII.
(Advances in experimental medicine and biology; v. 183)
"Proceedings of the Eighth International Symposium on Drugs Affecting Lipid
Metabolism, held July 27-30, 1983, in Philadelphia, Pennsylvania" - T.p. verso.
Includes bibliographies and indexes.
I. Atherosclerosis - Congresses. 2. Blood lipids - Metabolism - Disorders - Con
gresses. 3. Antilipemic agents-Congresses. I. Kritchevsky, David, 1920- . II.
Holmes, William L., 1918- . III. Paoletti, Rodolfo. IV. Title. V. Series. [DNLM: I.
Antilipemic Agents - congresses. 2. Arteriosclerosis - congresses. 3. Lipids - metab
olism - congresses. 4. Lipoproteins - metabolism - congresses. 5. Metabolism - drug
effects-congresses. WI AS559 v. 183/ QU 85 1596 1983d]
RC692.154 1983 616.1'36 84-26547
ISBN-13 :978-1-4612-9493-1 e-ISBN-13:978-1-4613-2459-1
DOl: I 0.1007/978-1-4613-2459-1
Proceedings of the Eighth International Symposium on Drugs Affecting
Lipid Metabolism, held July 27-30, 1983, in Philadelphia, Pennsylvania
© 1985 Plenum Press, New York
Softcover reprint of the hardcover 18t 1985
A Division of Plenum Publishing Corporation
233 Spring Street, New York, N.Y. 10013
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted,
in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording, or otherwise, without written permission from the Publisher
PREFACE
The Proceedings of the Eight International Symposium
on Drugs Affecting Lipid Metabolism (8th D.A.L.M.) is the
subject of this volume. Since the first symposium in 1960,
each successive meeting has broken new ground in the field
of pharmacological control of lipid levels - offering new
and stimulating insights and exposing the audience to the
state of the art. The field has progressed sufficiently
to permit discussion of the cellular biology of athero
sclerosis. The opening session was devoted to pathology,
macrophages, lipoproteins and their receptors and choles
terol ester metabolism. Because of the recent emergence
of new apolipoprotein technology, a workshop devoted sole
ly to apolipoprotein methodology was introduced followed
by a plenary session devoted to their metabolism and
structure.
Another rapidly developing area of atherosclerosis
research is non-invasive assessment of this condition.
Accordingly, a session was devoted to new techniques
for this research modality. The final plenary sessions
were devoted to the roles of drugs and diet in
athero~
- cause, treatment and mechanisms of action.
scl~rosis
The meeting was summarized by Dr. O.J. Pollak, one of the
"founding fathers" of this field. There were nine sessions
of proffered papers whose abstracts appear in this volume.
In addition, special workshops (to be reported elsewhere)
were devoted to several drugs including Oiyzanol, Probucol
and Etofibrate.
We are grateful for the interest of the organizations
whose generous support contributed to the success of the
meeting. The sponsorship of the Lorenzini Foundation was
especially appreciated. The success of this meeting was
due, in part, to the strong support of the local organiz
ing committee. We are deeply indebted to Mrs. Frances
Murray Nigro for her efficient and cheerful handling of
v
PREFACE
the duties of the secretariat. The smoothness of this
critical operation was principally instrumental for the
success of the symposium. We also wish to thank Mrs.
Edith Basedow Pappas for her expert help in the prepara
tion of this volume.
David Kritchevsky
William L. Holmes
Rudolfo Paoletti
We gratefully acknowledge support fran the following canpanies:
Abbott laboratories ~rrell-Dow Phannaceuticals, Inc.
American Cyanamid Canpany ~z and Canpany
Ayerst laboratories Nu-Check-Prep, Inc.
Best Foods, CPC International OtsukaPhannaceutical Canpany, Ltd.
Burroughs Wellcone Company Parke-Davis, Warner-Lambert Canpany
Daiichi Pure Chemicals Conpany, Ltd. The Procter & Ganble Company
Jolmson & Jolmson A.H. Robins Canpany
Kraft, Inc. G. D. SearI e and Canpany
Eli lilly and Corrpany ~th Kline and French laboratories
NcNeil Pharmaceutical Upjolm ~y
vii
IN'IERNATIOOAL ADVISORY CXM1ITlEE:
Dr. S. Bergstran (Sweden) Dr. W.L. Holmes (U.S.A.)
Dr. L.A. Carlson (Sweden Dr. D. Kritchevsky (U.S.A.)
Dr. G. Fass:ina (Italy) Dr. R. Paoletti (Italy)
Dr. A.M. Gotto (U.S.A.) Dr. G. Schettler (Germany)
Dr. S.M. Grundy (U.S.A.) Dr. C. Sirtori (Italy)
ORGANIZIN; CCM1ITlEE:
Dr. N. DiTullio Dr. D. Kritchevsky
Dr. W. L. Holmes Dr. J. Plostnieks
Dr. D.M. Klurfeld Dr. G. Reichard
SCIENTIFIC SECRETARIES:
Dr. W.L. Holmes
Dr. R. Paoletti
PRCX;RAM CHAIRMAN:
Dr. D. Kritchevsky
SPCNSORED BY:
COUNCIL ON AR1ERIOSCIEROSIS OF 1HE AMERICAN HEART
ASSOCIATION
FOODAZIONE GIOVANNI LORENZINI
ix
CONTENTS
CELLULAR BIOLOGY OF ATHEROSCLEROSIS
The Cellular Pathobiology of Atherosclerosis
in 1983 ..................................... 1
R.W. Wissler
Secretory Functions of the Mononuclear
Phagocyte ................................... 17
W.A. Scott, N.A. Pawloswki, E.B. Cramer
and Z.A. Cohn
Risk Factors for the Development of
Premature Cardiovascular Disease............ 27
H.B. Brewer, Jr., D.L. Sprecher, R.E. Gregg
and J.M. Hoeg
Fate of Cholesteryl Linoleyl Ether Injected
into Rats as Chylomicrons,
Acetylated LDL and HDL ......... ............. 37
Y. Stein and O. Stein
Hypertriglyceridemia: Lipoprotein Receptors
and Atherosclerosis......................... 47
S.H. Gianturco, A.M. Gotto, Jr.
and W.A. Bradley
Hypertriglyceridemia and Atherosclerosis:
Analysis of an Abnormal Lipoprotein
System and Potential Beneficial Effects
of Triglyceride Lowering Therapy...... ...... 73
S. Eisenberg
xi
xii CONTENTS
APOLIPOPROTEINS
The Role of Hydrophobicity in the Structure
of the Human Plasma Lipoproteins. ....... .... 85
H.J. Pownall and A.M. Gotto, Jr.
Metabolism of Apolipoproteins and the
Metabolic Heterogeneity of
Apo B in the Rat ............................ 99
J.B. Marsh
Proapolipoprotein A-I Metabolism in the
Human and the Rat ........................... 113
G. Ghiselli and B.C. Sherrill
Isolation and Characterization of the
Apolipoprotein Genes ........................ 121
J.L. Breslow
Apoprotein Measurements ........................... 125
J.J. Albers
Use of Monoclonal Antibodies in Studies of
Lipoprotein Structure and Function .......... 135
G. Schonfeld, M.J. Tikkanen and K-S. Hahm
Apolipoprotein E: Receptor Binding Properties 159
K.H. Weisgraber, T.L. Innerarity,
S.C. Rall, Jr. and R.W. Mahley
Apolipoprotein E Mutants, Hyperlipidemia
and Arteriosclerosis ........................ 173
G. Utermann
NONINVASIVE ASSESSMENT OF ATHEROSCLEROSIS
Noninvasive Assessment of Atherosclerosis
in Nonhuman Primates ........................ 189
M.G. Bond, S.K. Wilmoth, J.F. Gardin,
R.W. Barnes and J.K. Sawyer
Noninvasive Assessment of Atherosclerosis:
Studies in Man .............................. 197
R.J. Lusby
Noninvasive Atherosclerosis Assessment for
Controlled Clinical Trials .................. 209
D.H. Blankenhorn