Apolipoprotein Mimetics in the Management of Human Disease

202 Pages·2015·4.784 MB·English

by  G.M. Anantharamaiah, Dennis Goldberg (eds.)

G.M. Anantharamaiah
Dennis Goldberg Editors
Apolipoprotein
Mimetics in the
Management of
Human Disease
Apolipoprotein Mimetics in the Management
of Human Disease

G.M. Anantharamaiah (cid:129) Dennis Goldberg
Editors
Apolipoprotein Mimetics
in the Management
of Human Disease

Adis
Editors
G.M. Anantharamaiah Dennis Goldberg
Department of Medicine LipimetiX Development, LLC
University of Alabama School of Medicine Natick , MA
Birmingham , AL USA
USA
ISBN 978-3-319-17349-8 ISBN 978-3-319-17350-4 (eBook)
DOI 10.1007/978-3-319-17350-4
Library of Congress Control Number: 2015942492
Springer Cham Heidelberg New York Dordrecht London
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Pref ace
A polipoproteins on the surface of plasma lipoproteins are responsible for not only
solubilizing otherwise insoluble lipids but also are involved in the metabolism of
these lipoproteins via targeting to specifi c cell surface receptors and activation or
inhibition of lipolytic enzymes. While all of the apolipoproteins possess a common
lipid-associating structural motif, the amphipathic helix, each apolipoprotein is
unique in its properties and functions. Apolipoprotein A-I (apoA-1), the major pro-
tein component of high-density lipoproteins (HDL), was thought to be responsible
for the much of the anti-atherogenic properties of HDL. Attention was focused on
understanding the functionality of this apolipoprotein via the study of mutants that
decreased atherosclerosis is some populations. Clinical studies have been per-
formed with both recombinant human apolipoprotein A-I and certain mutants.
However, this has practical limitations due to the requirement of large amounts of
protein.
A lthough study of the model amphipathic helical peptides was initiated three
decades ago, the fi rst paper describing the ability of a small peptide consisting of
only 18 amino acids to inhibit the development of atherosclerosis was published in
the year 2001. Since then, the fi eld of apolipoprotein mimetics took off as several
laboratories within and outside the USA began designing and testing their pep-
tides in animal models for not only atherosclerosis but also for other lipid-mediated
diseases such as diabetes and Alzheimer’s disease. Recently, the receptor binding
domain of apolipoprotein E (apoE) was incorporated into the apoA-I mimetic pep-
tides to combine the plasma cholesterol lowering properties of apoE with the anti-
atherogenic properties of apoA-1. These new peptides are now considered as the
apoE mimetic peptides. Both the apoA-I mimetic and apoE mimetic peptides are
undergoing clinical evaluation.
This book compiles current knowledge on the studies done on apolipoprotein
mimetics from leading researchers in this fi eld. Its major aim is to present novel
v
vi Preface
ideas, highly unexpected mechanisms of action in animal models and even in initial
clinical studies in humans, which would lead to additional improvements in basic
and clinical research in biological science. This is the fi rst compendium of this
growing fi eld presented in the form of a book.
Birmingham, AL, USA G. M. Anantharamaiah
Natick, MA, USA Dennis Goldberg
Abbreviations
4F Peptide Ac-D-W-F-K-A-F-Y-D-K-V-A-E-K-F-K-E-A-F-NH
2
6F Peptide D-W-L-K-A-F-Y-D-K-F-F-E-K-F-K-E-F-F synthesized from
L-amino acids
ABCA1 ATP-binding cassette, sub-family A member 1
ABCG1 ATP-binding cassette, sub-family G member 1
ACS Acute coronary syndrome
AKT Protein kinase B
AMPK AMP-activated protein kinase
Apo Apolipoprotein
ApoA-I Apolipoprotein A-I
ApoA-II Apolipoprotein A-II
ApoC-III Apolipoprotein C-III
Arg1 Arginase 1
ATF3 Activating transcription factor 3
BMDM Bone marrow-derived macrophage
CBS Common beta subunit
CD Cluster of differentiation
CD14 Membrane (m) or soluble (s) pattern recognition receptor (cluster of
differentiation 14)
CER Ceramide
CETP Cholesterol ester transport protein
CHD Coronary heart disease
CLEC4a C-type lectin domain family 4 member A
CREB cAMP response element-binding protein
D-4F The 4F peptide synthesized from all D-amino acids
DCFA Dichlorodihydrofl uorescein diacetate
EM Electron microscopy
eNOS Endothelial constitutive nitric oxide synthase
EV Transgenic control tomato expressing a marker protein (β-glucuronidase)
FGF Fibroblast growth factor
HDL High-density lipoproteins
vii
viii Abbreviations
HO-1 Heme oxygenase 1
HPETE Hydroperoxyeicosatetraenoic acid
HPODE Hydroperoxyoctadecadienoic acid
HSPC Hematopoietic stem and progenitor cells
HUVEC Human umbilical vein endothelial cell
ICAM Intercellular adhesion molecule
IFN Interferon
IL Interleukin
iNOS Inducible nitric oxide synthase
IRF-5 Interferon regulatory factor 5
IRAK1 Interleukin-1 receptor-associated kinase 1
IRF Interferon regulatory factor
IVUS Intravascular ultrasound
JAK2 Janus kinase 2
KLF4 Kruppel-like factor 4
L-4F The 4F peptide synthesized from all L-amino acids
LCAT Lecithin/cholesterol acyltransferase
LAL Limulus amebocyte lysate
LBP Lipopolysaccharide binding protein
LDL Low-density lipoprotein
LDLR Low-density lipoprotein receptor
LKB1 Liver kinase B1
LPA Lysophosphatidic acid
LPS Lipopolysaccharide
LXRα Liver X receptor
Ly6C Lymphocyte antigen 6C
MβCD Methyl-β-cyclodextrin
MARCO Macrophage receptor with collagenous structure
MCP-1 Monocyte chemoattractant protein-1
MDM Monocyte-derived macrophage
MnSOD Manganese superoxide dismutase
MPO Myeloperoxidase
MRS Magnetic resonance spectroscopy
NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells
OCR Oxygen consumption rate
OVA Ovalbumin
PAF-AH Platelet-activating factor acetylhydrolase
PKA Protein kinase A
PON-1 Paraoxonase 1
PPARγ Peroxisome proliferator-activated receptor γ
RBC Red blood cells
RCT Reverse cholesterol transport
ROS Reactive oxygen species
RNS Reactive nitrogen species
S1P Sphingosine-1-phosphate
Abbreviations ix
SAA Serum amyloid A
SDS Sodium dodecyl sulfate
SM Sphingomyelin
SOCS1 Suppressor of cytokine signaling 1
STAT Signal transducer and activation of transcription
STAT3 Signal transducer and activator of transcription 3
TF Transferrin
Tg6F Transgenic tomato expressing the 6F peptide
TGF Transforming growth factor
TLR Toll-like receptor
TLR4 Toll-like receptor 4
TNF-α Tumor necrosis factor alpha
TRAF6 TNF receptor-associated factor 6
TTR Transthyretin
UAB University of Alabama at Birmingham
VCAM Vascular cell adhesion molecule
VCAM-1 Vascular cell adhesion molecule 1
VEGF Vascular endothelial growth factor
VLDL Very-low-density lipoproteins
VLDL-R VLDL receptor
WD Western diet
XO Xanthine oxidase