Pharmacological Control of Lipid Metabolism: Proceedings of the Fourth International Symposium on Drugs Affecting Lipid Metabolism held in Philadelphia, Pennsylvania, September 8–11, 1971

355 Pages·1972·32.14 MB·English

by  W. L. Holmes (auth.)

PHARMACOLOGICAL CONTROL
OF LIPID METABOLISM
ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY
Editorial Board:
Nathan Back Chairman, Department 01 Biochemical Pharmacology, School 01 Pharmacy,
State University 01 New York, Buffalo, New York
N. R. Di Luzio Chairman, Department 01 Physiology,
Tulane University School 01 Medicine, New Orleans, Louisiana
Alfred Gellhorn University 01 Pennsylvania Medical School, Philadelphia, Pennsylvania
Bernard Halpern College de France,
Director 01 the Institute 01 Immuno.Biology, Paris, France
Ephraim Katchalski Department 01 Biophysics, The Weizmann Institute 01 Science,
Rehovoth, Israel
David Kritchevsky Wistar Institute, Philadelphia, Pennsylvania
Abel Lajtha New York State Research Institute lor Neurochemistry and Drug Addiction,
Ward's Island, New York
Rodolfo Paoletti Institute 01 Pharmacology, University of Milan, Milan, Italy
Volume 1
THE RETICULOENDOTHELIAL SYSTEM AND ATHEROSCLEROSIS
Edited by N. R. Di Luzio and ~. Paoletti 0 1967
Volume 2
PHARMACOLOGY OF HORMONAL POLYPEPTIDES AND PROTEINS
Edited by N. Back, L. Martini, and R. Paoletti 0 1968
Volume 3
GERM·FREE BIOLOGY: Experimental and Clinical Aspects
Edited by E. A. Mirand and N. Back 0 1969
Volume 4
DRUGS AFFECTING LIPID METABOLISM
Edited by W. L. Holmes, L. A. Carlson, and R. Paoletti 0 1969
Volume 5
LYMPHATIC TISSUE AND GERMINAL CENTERS IN IMMUNE RESPONSE
Edited by L. Fiore.Donati and M. G. Hanna, Jr. 0 1969
Volume 6
RED CELL METABOLISM AND FUNCTION
Edited by George J. Brewer 0 1970
Volume 7
SURFACE CHEMISTRY OF BIOLOGICAL SYSTEMS
Edited by Martin Blank 0 1970
Volume 8
BRADYKININ AND RELATED KININS: Cardiovascular, Biochemical, and
Neural Actions
Edited by F. Sicuteri, M. Rocha e Silva, and N. Back 0 1970
Volume 9
SHOCK: Biochemical, Pharmacological, and Clinical Aspects
Edited by A. Bertelli and N. Back 01970
Volume 10
THE HUMAN TESTIS
Edited by E. Rosemherg and C. A. Paulsen 01970
Volume 11
MUSCLE METABOLISM DURING EXERCISE
Edited by B. Pernow and B. Sabin 0 1971
Volume 12
MORPHOLOGICAL AND FUNCTIONAL ASPECTS OF IMMUNITY
Edited by K. Lindahl·Kiessling, G. AIm, and M. G. Hanna, Jr. 0 1971
Volume 13
CHEMISTRY AND BRAIN DEVELOPMENT
Edited by R. Paoletti and A. N. Davison· 1971
Volume 14
MEMBRANE·BOUND ENZYMES
Edited by G. Porcellati and F. di Jeso • 1971
Volume 15
THE RETICULOENDOTHELIAL SYSTEM AND IMMUNE PHENOMENA
Edited by N. R. Di Luzio and K. Flemming· 1971
Volume 16A
THE ARTERY AND THE PROCESS OF ARTERIOSCLEROSIS: Pathogenesis
Edited by Stewart Wolf· 1971
Volume 16B
THE ARTERY AND THE PROCESS OF ARTERIOSCLEROSIS: Measurement and
Modification
Edited by Stewart Wolf· 1972
Volume 17
CONTROL OF RENIN SECRETION
Edited by Tatiana A. Assaykeen ·1972
Volume 18
THE DYNAMICS OF MERISTEM CELL POPULATIONS
Edited by Morton W. Miller and Charles C. Kuehnert. 1972
Volume 19
SPHINGOLIPIDS, SPHlNGOLlPIDOSES AND ALLIED DISORDERS
Edited by Bruno W. Volk and Stanley M. Aronson • 1972
Volume 20
DRUG ABUSE: Nonmedical Use of Dependence.Producing Dru!!8
Edited by Simon Btesh • 1972
Volume 21
VASOPEI'TIDES: Chemistry, Pharmaeolo!':y, and l'athophysiolop:y
Edited by N. Ba<'k and F. Sicuteri • 1972
Volume 22
COMPARATIVE PATHOPHYSIOLOGY OF CIRCULATORY DISTURBANCES
Edited by Colin M. Bloor. 1972
Volume 23
THE FUNDAMENTAL MECHANISMS OF SHOCK
Edited by Lerner B. Hinshaw and Barbara G. Cox. 1972
Volume 24
THE VISUAL SYSTEM: Neurophysiology, Biophysics, and Their Clinical Applieations
Edited by G. B. Arden • 1972
Volume 25
GLYCOLIPIDS, GLYCOPROTEINS, AND MUCOPOLYSACCHARIDES
OF THE NERVOUS SYSTEM
Edited by Vittorio Zambotti, Guido Tettamanti, and Mariagrazia Arrigoni • 1972
Volume 26
PHARMACOLOGICAL CONTROL OF LIPID METABOLISM
Edited by William L. Holmes, Rodolfo Paoletti,
and David Kritchevsky • 1972
Volume 27
DRUGS AND FETAL DEVELOPMENT
Edited by Marcus A. Klingberg, Armand Abramovici, and Juan Chemke • 1972
Volume 28
HEMOGLOBIN AND RED CELL STRUCTURE AND FUNCTION
Edited by George J. Brewer • 1972
PHARMACOLOGICAL
CONTROL OF
LIPID METABOLISM
Proceedings of the Fourth International Symposium on
Drugs Affecting Lipid Mctaholism held in Philadelphia,
Pennsylvania, Septemher 8-11, 1971
Edited by
Willianl L. HolnleS
Diredor, Division of Researth
Lankenau Hospital
Philadelphia, Pennsylvania
Rodolfo Paoletti
Director, Institute of Pharmacology and Pharmacognosy
University of Milan
Milan, Italy
and
David I(ritchevsky
Member, The Wi star Institute of Anatomy and Biology
Philadelphia, Pennsylvania
~ SPRINGER SCIENCE+BUSINESS MEDIA, LLC 1972
Symposium sponsored hy
Council on Arteriosclerosis
International Society of Cardiology
Scientific Council on Arteriosclerosis and Ischemie Heart Disease
International Society for Biochemical Pharmacology
The Heart Association of Southeastern Pennsylvania
Lihrary of Congress Catalog Card Numher 72-82746
ISBN 978-1-4684-7549-4 ISBN 978-1-4684-7547-0 (eBook)
DOI 10.1007/978-1-4684-7547-0
© 1972 Springer Science+Business Media New York
Originally published by Plenum Press, New York in 1972
Softcover reprint ofthe hardcover lst edition 1972
AU rights reserved
No part of this puhlication may he reproduced in any form without
written permission from the puhlisher
INTERNATIONAL ORGANIZING COMMITTEE:
S. BergstroITl - Sweden
L. A. Carlson - Sweden
S. Garattini - Italy
W. L. HolITles -U.S.A.
D. Kritchevsky - U. S. A.
M. F. Oliver - U.K.
R. Paoletti - Italy
G. Schettler - GerITlany
D. Steinberg - U. S. A.
LOCAL ORGANIZING COMMITTEE:
G. A. Braun
N. W. Di Tullio
W. L. HolITles
D. Kritchevsky
G. A. Reichard, Jr.
J. J. Spitzer
SCIENTIFIC SECRET ARIES:
W. L. HolITles, Philadelphia, Pa. (U. S. A.)
R. Paoletti, Milan (Italy)
PROGRAM CHAIRMAN:
D. Kritchevsky, Philadelphia, Pa. (U. S. A. )
vii
ACKNOWLEDGMENTS
The Organizing Connnittee gratefully acknowledges the con
tributions of the following organizations:
Ayerst Laboratories New York, New York
Baxter Laboratories Morton Grove, Illinois
Best Foods Research Center Union, New Jersey
Bristol Laboratorie s Syracuse, New York
CIBA Pharmaceutical Company Summit, New Jersey
Dow Chemical Company Zionsville, Indiana
Geigy Pharmaceuticals Ardsley, New York
Hoechst Pharmaceutical Company Somerville, New Jersey
Hoffmann-LaRoche, Inc. Nutley, New Jersey
Eli Lilly and Company Indianapolis, Indiana
McNeil Laboratories, Inc. Fort Washington, Pennsylvania
Mead Johnson Research Center Evansville, Indiana
Merck Sharpe & Dohme Rahway, New Jersey
Pfizer Pharmaceuticals Groton, Connecticut
A. H. Robins Company Richmond, Virginia
Sandoz Pharmaceuticals Hanover, New Jersey
Schering Corporation Bloomfield, New Jersey
G. D. Searle & Company Chicago, Illinois
Smith Kline & French
Laboratories Philadelphia, Pennsylvania
Sumitomo Chemical Company, Ltd. Osaka, Japan
The Upjohn Company Kalamazoo, Michigan
Wallace Laboratories Cranbury, New Jersey
Warner-Lambert Pharmaceutical
Company Morris Plains, New Jersey
The generosity of these organizations made it possible for
us to arrange this Symposium, which was attended by more than
four hundred scientists working on problems of lipid metabolism.
The Or ganizing Committee
viii
PREFACE
This Symposium was the fourth in a series which began in
Milan, Italy, in 1960. Each meeting has introduced or developed
some new concepts in the areas of lipid metabolism and drugs.
The meetings have served as a springboard for new ideas which
have, between meetings, become accepted and exploited. This
meeting has been no exception. Principal among the many new
concepts discussed were lipoprotein synthesis and metabolism,
apoprotein structure and function, whole body metabolism of
cholesterol, and aspects of myocardial and aortic metabolism.
The Symposium also included a summary of current thought on
management of hyperlipemias and atherosclerosis. Data on
more than 30 drugs were introduced and discussed. We have
every expectation that the next Symposium will include material
which is now only in the formative stage.
The Organizing Committee would like to acknowledge the
invaluable assistance of Miss Mary Constant, Mr. Ralph H.
Hollerorth, Mrs. Carolyn P. Hyatt and Miss Jane T. Kolimaga,
whose efforts contributed significantly (p < .001) to the success
of this Symposium.
W. L. Holmes
R. Paoletti
D. Kritchevsky
ix
CONTENTS
Opening Remarks .. 1
W. L. Holme s
NEWER DEVELOPMENTS IN LIPID BIOCHEMISTRY
Synthesis and Secretion of Plasma Lipoproteins. . . . .. 7
R. L. Hamilton
The Apolipoproteins. . . . . . . . . . . .. 25
D. S. Fredrickson, S. E. Lux, and P. N. Herbert
Mechanisms of Hyperlipoproteinemia 57
R. J. Havel
Clearing Factor Lipase and Its Role in the Regulation
of Triglyceride Utilization. Studies on
the Enzyme in Adipose Tissue. . • . . . . .. 71
D. S. Robinson and D. R. Wing
Hormonal Control of Lipolysis in Adipose Tissue. . . .. 77
D. Steinberg
The Role of Cyclic 3' 5' -AMP and Its Derivatives in
Lipid and Carbohydrate Metabolism 89
o
R. Paoletti
Biochemical Changes in the Artery Wall during Genesis
and Regression of Atheromatous Lesions 91
H. B. Lofland, Jr., R. W. St. Clair and
T. B. Clarkson
xi