HDL Handbook (eBook)

Front Cover 
1 
The HDL Handbook 4
Copyright 
5 
Contents 6
Preface 8
Contributors 10
Chapter 1 
14 
Introduction 14
Molecular biology and structure of phospholipid transfer protein 15
PLTP-mediated lipid transfer 17
PLTP-mediated HDL remodeling 17
Genetically modified animals 18
PLTP and atherosclerosis in humans 22
Conclusion 23
References 23
Chapter 2 
30 
Introduction 30
Molecular biology 31
Effect of CETP action on HDL structure 33
Effect of CETP activity on plasma HDL levels and atherosclerotic disease 33
Effect of CETP activity on HDL function and consequences for atherosclerotic disease 35
Polymorphisms of the CETP gene and interactions between environmental influences and HDL 39
Inhibitors of CETP activity as therapy 40
Conclusion 41
References 41
Chapter 3 
48 
Introduction 48
Structure of CETP 50
Regulation of CETP expression 50
Function of CETP 51
Role of CETP in apoE-rich HDL formation 54
Molecular genetics and the ethnic difference in the frequency of human CETP deficiency 55
Clinical chemistry of LDL-cholesterol and HDL-cholesterol in CETP deficiency 56
Epidemiology of increased HDL cholesterol levels and CETP deficiency 57
Development of a CETP inhibitor 59
Role of CETP in aging and longevity 61
Role of CETP in dyslipidemia associated with diabetes and metabolic syndrome 63
Clinical Trials of CETP inhibitors 64
Low CETP status, genetic or environmental? 64
References 64
Chapter 4 
74 
Influence of aging on the reverse cholesterol transport pathway 74
Influence of hormones on the reverse cholesterol transport pathway 74
Influence of physical activity on the reverse cholesterol transport pathway 78
Influence of diet on the reverse cholesterol transport pathway 79
Influence of alcohol consumption on the reverse cholesterol transport pathway 80
Influence of smoking on the reverse cholesterol transport pathway 81
Influence of postprandial state on the reverse cholesterol transport pathway 82
Conclusion 84
Acknowledgments 84
References 84
Chapter 5 
90 
Introduction 90
HDL - structure, heterogeneity and anti-atherogenic properties 91
Paraoxonase-1 (PON1) 95
The association between PON1 and HDL 96
Conclusion 105
References 105
Chapter 6 
112 
Introduction 112
PON1 as a promiscuous human plasma enzyme 115
HDL molecular environment of PON1 119
Impediments for studying the passenger PON1 andnbspthe vehicle HDL 121
PON1 activity in normal HDL conditions 125
PON1 activity in altered HDL conditions 128
PON1 activity in therapeutic HDL 131
Conclusion 134
References 135
Chapter 7 
146 
Introduction 146
GENOMIC AND PROTEIN STRUCTURE OF APOA-I 147
PHYSIOLOGICAL FUNCTIONS OF APOA-I 147
APOA-I DEFICIENCIES WITH LARGE DELETION, NONSENSE OR FRAMESHIFT MUTATIONS 148
APOLIPOPROTEIN A-I VARIANTS 152
REFERENCES 157
Chapter 8 
166 
Overview 166
Role of SR-BI in HDL metabolism, atherosclerosis and coronary heart disease - studies from genetically altered mice 166
SR-BI mediated HDL lipid uptake and efflux 168
Cellular Biology of SR-BI: Localization 169
SR-BI-mediated endocytosis of HDL 172
Multimerization of SR-BI 173
PDZK1, an adaptor protein that binds to SR-BI's carboxy terminal cytoplasmic tail 173
Regulation of SR-BI 174
Molecular mechanisms of HDL-mediated signaling 174
Protein kinase C (PKC) pathway 175
Mitogen activated protein kinase (MAPK) pathway 176
PI3K/Akt Pathway 178
Conclusions 181
References 181
Chapter 9 
192 
Introduction 192
Heterogeneity of HDL 193
Physiological mechanisms of protective action of HDL and apoA-I 194
Pro-inflammatory HDL 196
HDL therapy 196
Structural characteristics of apoA-I 198
ApoA-I mimetic peptides 198
ApoE mimetic peptides 203
Other apo-mimetic peptides 204
Conclusion 204
References 205
Chapter 10 
212 
Introduction 212
ABCA1-mediated cholesterol efflux 212
ABCG1-mediated cholesterol efflux 214
Cellular mechanisms of cholesterol efflux via ABCA1 and ABCG1 215
The role of ABCA1- and ABCG1-mediated cholesterol efflux pathways in atherosclerosis 217
A potential role of HDL, ABCA1 and ABCG1 in macrophage apoptosis and inflammation in plaques 218
A potential role of HDL and ABCG1 in endothelial function 220
Conclusion and Perspective 221
References 221
Chapter 11 
228 
Introduction 228
Structural alterations in HDL components by oxidation 229
Functional alterations in HDL by oxidation 237
Conclusion 243
References 243
Chapter 12 
256 
Introduction 256
Characteristics of HDL 257
HDL subfractions 259
Plasma prebeta1-HDL concentration in various disorders 264
Turnover of prebeta1-HDL in human plasma 267
Conclusions 268
References 269
Chapter 13 
274 
Introduction 274
Evidence of oxidized HDL in tissue andnbspcirculation 275
Measurement of oxidized HDL in clinical samples 276
Other methods 278
Considerations for HDL oxidation in vitro 278
Clinical significance of oxidized HDL measurement 279
Conclusion 283
References 284
Index 290