Lipoprotein Deficiency Syndromes

299 Pages·1986·7.785 MB·English

by  Ernst J. Schaefer, Judith R. McNamara, Carol J. Mitri, Jose M. Ordovas (auth.), Aubie Angel, Jiri Frohlich (eds.)

LIPOPROTEIN
DEFICIENCY
SYNDROMES
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, _W istar Institute
ABEL LAJTHA, Rockland Research Institute
RODOLFO PAOLETTI, University of Milan
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LIPOPROTEIN
DEFICIENCY
SYNDROMES
Edited by
Aubie Angel
Institute of Medical Sciences
University of Toronto
Toronto, Ontario, Canada
and
Jiri Frohlich
Shaughnessy Hospital
University of British Columbia
Vancouver, British Columbia, Canada
Springer Science+Business Media, LLC
Library of Congress Cataloging in Publication Data
International Conference on Lipoprotein Deficiency Syndromes (1985: Vancouver,
B.C.)
Lipoprotein deficiency syndromes.
(Advances in experimental medicine and biology; v. 201)
"Proceedings of an International Conference on Lipoprotein Deficiency Syndromes,
held in conjunction with the Tenth Canadian Lipoprotein Conference, May 13-14,
1985, in Vancouver, British Columbia, Canada"-T.p. verso.
Includes bibliographies and index.
1. Hypolipoproteinemia-Congresses. I. Angel, Aubie. 11. Canadian Lipoprotein
Conference (10th: 1985: Vancouver, B.C.) III. Tide. IV. Series. [DNLM: 1. Lipo
proteins-deficiency-congresses. Wl AD559 v.201 / QU 85 I5917L 1985]
RC632.H92I57 1985 616.3'99 86-16852
ISBN 978-1-4684-1264-2
ISBN 978-1-4684-1264-2 ISBN 978-1-4684-1262-8 (eBook)
DOI 10.1007/978-1-4684-1262-8
Proceedings of an International Conference on Lipoprotein Deficiency Syndromes,
held in conjunction with the tenth Canadian Lipoprotein Conference,
May 13-14, 1985, in Vancouver, British Columbia, Canada
© 1986 Springer Science+Business Media New York
Orginally published by Plenum Press in 1986
Softcover reprint of the hardcover 1s t edition 1986
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
Current interest in lipoprotein deficiency states stems from the
growing realization of their importance in the etiology of premature
coronary heart disease. While hypercholesterolemia and coronary heart
disease risk are strongly correlated in their etiologic relationship, it
is becoming equally clear that deficiencies in HDL, whether congenital or
acquired, also enhance the risk for the future development of coronary
atherosclerosis. This has led to renewed attention to the lipid
hypothesis and realization of the fact that each lipoprotein class and
apoprotein species has specific functions in the transport and cellular
uptake of various lipids.
It is a truism that a biochemical correlate of disease once identified
is subsequently recognized with increasing frequency in clinical medicine.
The story of HDL was no exception. Indeed hypoalphalipoproteinemia
appears to be a disease of high prevalence approaching and perhaps even
exceeding that of familial hypercholesterolemia. Its clinical signifi
cance escaped our notice for many years largely due to a heavy emphasis on
hypercholesterolemia and to difficulties in measuring HDL reliably.
Recognizing that clinical assessment of patients suspected of
lipoprotein disorders requires understanding of newer concepts, we thought
it timely to assemble leaders in this field to highlight advances in
understanding the lipoprotein deficiency syndromes and their etiologic
mechanisms. The four chapters of this book represent areas of major
interest. We have avoided the historic context and emphasized relation
ships between lipoprotein deficiencies, their molecular mechanisms and
clinical correlations. The first chapter focuses on the relationship
between plasma HDL deficiency and atherosclerosis. Clinically relevant
relationships are identified, and various disease states commonly
associated with premature coronary disease are covered. Hypoalphalipo
proteinemia is not a single disease but a multitude of syndromes with
varied etiologies. The second chapter explores these syndromes discussing
both the common autosomal dominant disorder and rare, mostly recessive,
diseases differing in molecular etiologies. In chapter three lecithin:
cholesterol acyl-transferase (LCAT), the enzyme responsible for plasma
cholesterol esterification is discussed in detail. The role of LCAT in
the context of cellular cholesterol efflux is also addressed. Numerous
hypertriglyceridemic syndromes are associated with deficiencies or defects
in lipoprotein lipase or hepatic lipase activity, apoprotein CII and apo
E. These are covered in chapter four. Finally, scattered throughout the
book are papers with recent insights in the molecular biology of
apoprotein synthesis and metabolism. Here the molecular etiology of
lipoprotein deficiency syndromes are explored at the genomic level.
This area will be of particular interest to those wishing to
understand the molecular biology of lipoprotein disorders.
v
We believe that this book will be of use to clinical lipidologists,
resident trainees and research fellows as well as graduate students
interested in both research and clinical aspects of lipoprotein
metabolism.
A. Angel
J. Frohlich
VI
ACKNOWLEDGMENTS
An International Conference on Lipoprotein Deficiency Syndromes was
held in conjunction with the Tenth Canadian Lipoprotein Conference on May
13 to 15, 1985 at the University of British Columbia, Vancouver, B.C.,
Canada. This book contains the manuscripts presented by guest faculty,
who are leaders in the the area of lipoprotein deficiency diseases and
their cellular and molecular biology. We gratefully acknowledge the
principal sponsorship of British Columbia and Canadian Heart Foundations
and Bristol Laboratories of Canada.
The following Companies also supported the meeting; Abbott
Laboratories, Beckman, Fisher Scientific, Herdt & Chanton, Hoechst,
Hoffmann-La Roche, Kodak Company, Merck Frosst, Miles Laboratories,
Parke-Davis, Pfizer, Roche Laboratories, Sandoz, Searle, CIBA
Laboratories.
Finally, we are particularly indebted to Dr. Hayden Pritchard and Ms.
Lori DiMonte for assisting in the development of the meeting. We also
thank Ms. Lori DiMonte for organizing and preparing the manuscripts for
publication.
A. Angel
J. Frohlich
~i
CONTENTS
CHAPTER ONE: LIPOPROTEIN DEFICIENCY AND ATHEROSCLEROSIS
GENETIC HIGH DENSITY LIPOPROTEIN DEFICIENCY STATES AND
ATHEROSCLEROS IS. • . • • . • • . • • • • • • • • • • • • . . • • • . • • • • • . . • • • . . • • . • . • • . 1
E.J. Schaefer, J.R. McNamara, C.J. Mitri, and J.M. Ordovas
METABOLIC INTERRELATIONSHIPS OF HDL SUBCLASSES...................... 17
R.M. Krauss and A.V. Nichols
SPECIATION OF HDL................................................... 29
J.P. Kane
MODIFICATIONS AND DEGRADATION OF HIGH DENSITY LIPOPROTEINS.......... 37
A. Angel and B. Fong
EFFECT OF DIABETES MELLITUS AND END-STAGE RENAL DISEASE ON HDL
METABOLISM. • . • • . . • . • . . • • • • . . • • • . . . . . . • • . . . . • • • • . . • • • . • • • • • • • . • . 51
M.H. Tan
HDL BINDING TO HUMAN ADIPOCYTE PLASMA MEMBRANES: REGIONAL VARIATION
IN OMENTAL AND SUBCUTANEOUS DEPOTS............................. 61
B. Fong, A. Salter, J. Jimenez, J.P. Despres, and A. Angel
CLINICAL, NUTRITIONAL AND BIOCHEMICAL CONSEQUENCES OF APOLIPOPROTEIN
B DEFICIENCY.. .•. .••..•••• .•••••••• ••• •••••••••••• •••••••••.•.• 67
H.J. Kayden and M.G. Traber
CHAPTER TWO: HYPOALPHALIPOPROTEINEMIA SYNDROMES
FAMILIAL HYPOALPHALIPOPROTEINEMIA................................... 83
C.J. Glueck, M.A. MeIser, I.B. Borecki, J.L.H.C. Third, D.C. Rao,
and P.M. Laskarzewski
A FAMILY STUDY OF HYPOALPHALIPOPROTEINEMIA.......................... 93
C. Vergani, A.L. Catapano, and A. Sidoli
APOPROTEIN A-I AND LECITHIN: CHOLESTEROL ACYLTRANSFERASE IN A PATIENT
WITH TANGIER DISEASE.......................................... 105
P.H.Pritchard and J. Frohlich
SEVERE HYPOALPHALIPOPROTEINEMIA INDUCED BY A COMBINATION OF PROBUCOL
AND CLOFIBRATE................................................ III
J. Davignon, A.C. Nestruck, P. Alaupovic, and D. Bouthillier
ix
CONTROL OF PLASMA HDL LEVELS AFTER PLASMAPHERESIS................... 127
G.R. Thompson and A. Jadhav
CLINICAL SYNDROME AND LIPID METABOLISM IN HEREDITARY DEFICIENCY OF
APOLIPOPROTEINS A-I AND C-III, VARIANT I ••••••••••••••••••••••• 137
R.A. Norum, T.M. Forte, P. Alaupovic, and H.N. Ginsberg
THE MOLECULAR BIOLOGY OF HUMAN APO A-I, APO A-II, APO C-II AND
APO B......................................................... 151
S.W. Law, K.J. Lackner, S.S. Fojo, A. Hospattankar, J.C. Monge,
and H.B. Brewer, Jr.
CHAPTER THREE: LCAT and CHOLESTEROL TRANSPORT
LECITHIN: CHOLESTEROL ACYLTRANSFERASE, A REVIEW AND IMMUNOCHEMICAL
STUDIES. • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • 163
Y.L. Marcel, C.A. Vezina, P.K. Weech, F. Terce, and R.W. Milne
LECITHIN: CHOLESTEROL ACYLTRANSFERASE DEFICIENCY SyNDROMES.......... 181
J. Frohlich and R. McLeod
CHOLESTEROL EFFLUX: MECHANISM AND REGULATION........................ 195
G.H. Rothblat and M.C. Phillips
INHIBITION AND ACTIVATION OF CHOLESTERYL ESTER TRANSFER AND ITS
SIGNIFICANCE IN PLASMA CHOLESTEROL METABOLISM................. 205
C.J. Fielding
CHAPTER FOUR: HYPERTRIGLYCERIDEMIA SECONDARY TO ENZYME OR APOPROTEIN
DEFICIENCY
APOLIPOPROTEIN C-II DEFICIENCy...................................... 211
W.C Breckenridge
PRIMARY LIPOPROTEIN LIPASE DEFICIENCy............................... 227
J.D. Brunzell, P.H. Iverius, M.S. Scheibel, W.Y. Fujimoto,
M.R. Hayden, R. McLeod, and J. Frohlich
THE GENETICS AND MOLECULAR BIOLOGY OF APOLIPOPROTEIN C-II........... 241
M.R. Hayden, C. Vergani, S.E. Humphries, L. Kirby, R. Shukin,
and R. McLeod
FAMILIAL HEPATIC LIPASE DEFICIENCy.................................. 253
J.A. Little and P.W. Connelly
THE APO E-SYSTEM: GENETIC CONTROL OF PLASMA LIPOPROTEIN
CONCENTRATION. •• • • • • •• • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • 261
G. Utermann
TYPE III HYPERLIPOPROTEINEMIA: A FOCUS ON LIPOPROTEIN
RECEPTOR-APOLIPOPROTEIN E2 INTERACTIONS....................... 273
T.L. Innerarity, D.Y. Hui, T.P. Bersot, and R.W. Mahley
THE ROLE OF APOLIPOPROTEIN E IN MODULATING THE METABOLISM OF
APOLIPOPROTEIN B-48 AND APOLIPOPROTEIN B-I00 CONTAINING
LIPOPROTEINS IN HUMANS........................................ 289
R.E. Gregg and B. Brewer, Jr.
INDEX. • • • • • • • • • • . • • • . • • • • • • • • . • • . • • • • . • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • 299
x
GENETIC HIGH DENSITY LIPOPROTEIN DEFICIENCY STATES AND ATHEROSCLEROSIS
Ernst J. Schaefer, Judith R. McNamara, Carol J. Mitri and
Jose M. Ordovas
Lipid Metabolism Laboratory, Human Nutrition Research Center
on Aging at Tufts University, 711 Washington Street
Boston, MA 02111
INTRODUCTION
High density. lipoprotein (HDL) as found in human plasma have a density
of 1.063-1.21 g/ml, and are composed (weight percent) of approximately 50%
protein, 25% phospholipid, 20% cholesterol, and 5% triglyceride (1).
Fluctuations in HDL levels have been associated mainly with alterations in
HDL2 (density, 1.063-1.125 g/ml), rather than HDL3 (density, 1.125-1.21
g/ml (2). Apolipoproteins (apo) A-I and A-II are the major proteins of
HDL. Minor constituents include apoB, apoC-I, apoC-II, apoC-III, apoD,
apoE, apoF, apoG, apoLp(a) (3-12). Apolipoprotein not only have struct
ural roles in HDL particles, but have other functions as well. ApoA-I and
apoC-I have both been reported to activate lecithin/cholesterol acyl trans
ferase (LCAT), while apoA-II has been reported to enhance hepatic lipase
activity (12-15). ApoC-II activates the enzyme lipoprotein lipase, while
apoC-III has been shown to inhibit hepatic chylomicron remnant uptake
(16,17). Both apoB and apoE can bind to the apoB,E receptor (LDL receptor)
on various cell surfaces, while apoE also binds to the liver apoE receptor,
which is essential for chylomicron remnant uptake (18,19). The low density
lipoprotein (LDL) receptor appears to be crucial for regulating LDL levels
in plasma, as well as for maintaining intracellular cholesterol homeostasis.
HDL particles can bind to specific sites on various cell surfaces (20).
Constitutents of HDL can be derived by direct synthesis of HDL parti
cles by the liver or the intestine, or as a result of the catabolism of
chylomicrons and very low density lipoproteins (VLDL) (21-31). HDL can
also pick up lipid constituents, especially free cholesterol, from
peripheral cells. Free cholesterol, apolipoproteins, and the polar head
groups of the phospholipids, are mainly on the surface of HDL particles,
while fatty acids of phospholipids, cholesterol ester and triglyceride are
found predominantly in the core.
After free cholesterol is picked up by HDL particles it is esterified
by the action of (LCAT), and is transferred to the core of the particle.
Cholesterol ester can then be transferred from HDL to other lipoproteins
by the action of a cholesterol ester transfer protein. Phospholipids can
also be exchanged to other lipoprotein particles. Triglyceride-rich
lipoproteins such as chylomicron remnants can serve as acceptors of
cholesterol ester from HDL. HDL3 can be converted to particles in the
HDL2 density region by picking up free cholesterol as well as phospholipid.