High Density Lipoproteins, Dyslipidemia, and Coronary Heart Disease (eBook)

Ernst J. Schaefer (Herausgeber)

eBook Download: PDF

2010 | 2010
XI, 205 Seiten
Springer New York (Verlag)
978-1-4419-1059-2 (ISBN)

Infos

This innovative book focuses on HDL and its relationships to triglyceride-rich particles. It is an excellent resource for educating physicians and scientists about dyslipidemia and HDL metabolism, including many exogenous substances which interact with and influence HDL.

Inhalt

Preface 5
Contents 7
Contributors 9
Introduction to High-Density Lipoprotein, Dyslipidemia, and Coronary Heart Disease 12
Introduction 12
Cholesterol Production 12
Cerebrotendinous Xanthomatosis 13
Familial Combined Hyperlipidemia 13
Cholesterol Absorption 14
Phytosterolemia 15
Plasma Lipids 15
Fatty Acids 15
Apolipoproteins 16
Apolipoprotein A-I 16
Apolipoprotein A-II 17
Apolipoprotein A-IV 17
Apolipoprotein A-V 18
Apolipoprotein B-100 18
Apolipoprotein B-48 18
The C Apolipoproteins 18
Apolipoprotein E 18
Plasma Lipoproteins 18
Chylomicrons 18
Abetalipoproteinemia 20
Hypobetalipoproteinemia 20
Severe Hypertriglyceridemia 20
Dysbetalipoproteinemia 21
Lipoproteins Containing Apolipoprotein B-100 22
Very-Low-Density Lipoproteins 22
Familial Dyslipidemia 23
Low-Density Lipoproteins 23
Familial Hypercholesterolemia 23
Lipoprotein (a) 23
Familial Lipoprotein (a) Excess 23
Conclusions 24
References 25
Regulation of ApoA-I Gene Expression and Prospects to Increase Plasma ApoA-I and HDL Levels 26
Transcriptional Regulation of the Human ApoA-I Gene in Cell Culture and in ApoA-I Transgenic Mice 26
References 34
High Density Lipoprotein Particles 36
Introduction 36
Separation of HDL Subclasses 36
HDL Structure 37
HDL Proteomics 40
Conclusions 42
References 43
The Kinetics and Remodeling of HDL Particles: Lessons from Inborn Errors of Lipid Metabolism 44
Introduction 44
Step 1: ApoA-I synthesis 45
Step 2: Cellular Cholesterol Efflux via ABCA1 46
Step 3: Cholesterol Esterification by LCAT 46
Step 4: LPL-Mediated Hydrolysis 47
Step 5: ABCG1-Mediated Cholesterol Efflux 48
Step 6: CETP Cycle 48
Step 7: HL-Mediated Lypolyses 50
Step 8: SR-B1 Cycle 51
Step 9: HDL Catabolism 51
Conclusions 53
References 53
HDL Structure, Function, and Antiinflammatory Properties 56
Introduction 56
Origins and Structure of HDL 56
Heterogeneity of HDL 56
HDL Remodeling and Its Relationship to Atherogenesis 57
Cardioprotective Properties of HDL Subpopulations 59
Increasing HDL Levels and Atherosclerosis 60
HDL and Inflammation 61
Antiinflammatory Properties of HDL: In Vitro Studies 61
Antiinflammatory Properties of HDL: In Vivo Studies 62
Concluding Remarks 62
References 62
Human Apolipoprotein A-I Deficiency 65
Introduction 65
Familial Apolipoprotein AI/CIII/AIV Deficiency 65
Familial Apolipoprotein AI/CIII Deficiency 65
Familial Apolipoprotein AI Deficiency 66
Case Study of Familial Apolipoprotein Deficiency 66
References 70
Human Apolipoprotein A-I Mutants 72
Introduction 72
Human ApoA-I Mutations Causing a Low-HDL Phenotype 72
Human ApoA-I Mutations Causing Hereditary Amyloidosis 76
References 77
ATP Binding Cassette A1 Transporter Function and Tangier Disease 79
Introduction 79
Pathologic Findings 79
Clinical Features of Tangier Disease 79
Lipoprotein Metabolism 81
Defective ABCA1 Transporter Function in Tangier Disease 83
Conclusions 84
References 84
The Role ABCG1 in Cellular Cholesterol Efflux: Relevance to Atherosclerosis and Endothelial Function 86
Introduction: ABC Transporters and Cholesterol Efflux Pathways 86
ABC Transporters and Atherosclerosis 86
HDL and Endothelial Functions 86
ABC Transporters and Endothelial Function 87
Abcg1 / Mice Show a Severe Defect in Endothelial-Dependent Vasorelaxation When Challenged with a Western-Type Diet or a 87
Clinical Relevance and the Gap in Understanding of HDL Biology 88
References 88
In Vitro Studies and Mass Flux of Cholesterol Between Serum and Macrophages 90
Introduction 90
Cholesterol Efflux to Serum 90
Impact of Cell Cholesterol Content on Cholesterol Flux 91
Net Flux of Cholesterol Mass 91
Relationship Between Efflux of Labeled Cholesterol and Reduction of Cell Cholesterol Mass 92
Relationship Between Transporter Expression and Mobilization of Cell Cholesterol Mass 92
Conclusion 93
References 94
Genetic LCAT Deficiency: Molecular Diagnosis, Plasma Lipids, and Atherosclerosis 96
Introduction 96
LCAT Gene Mutations and Lipid/Lipoprotein Phenotype 96
LCAT Gene Mutations and Atherosclerosis 98
Conclusions 99
References 100
Human Cholesteryl Ester Transfer Protein in Human HDL Metabolism 101
Introduction 101
Structure and Function of CETP 101
Genetics of Human CETP Deficiency 102
Discovery of Human CETP Deficiency 102
Phenotype of CETP Deficiency 103
LCAT Promotes FC Esterification in HDL3and CETP Transfers Newly Esterified CE from HDL3 to VLDL or Chylomicron 103
Atherogenicity of Plasma CETP 104
Relation to TG Metabolism 104
CETP Gene Mutations and Polymorphisms on Coronary Heart Disease Risk 104
Development of CETP Inhibitor and Its Phenotypic Similarity to Human CETP Deficiency 104
Effects on Cholesterol Efflux 105
Effects on ApoB-Containing Lipoproteins 105
Prospective (Table 2) 105
References 106
The HDL Receptor SR-BI 108
The HDL Receptor SR-BI Controls HDL Cholesterol Metabolism 108
Other Functions of SR-BI 109
SR-BI-Mediated Signaling and Endothelial Function 109
SR-BI and Adrenal Physiology 110
SR-BI and Microbial Pathogens 110
SR-BI and Atherosclerosis 110
PDZK1-Dependent Regulation of SR-BI 110
Human SR-BI 111
Conclusion 111
References 112
Genetic Loci Influencing Plasma High Density Lipoprotein Cholesterol Concentrations in Humans 115
Introduction 115
Single Cohort GWAS for HDL Cholesterol 115
Multiple Cohort GWAS for HDL Cholesterol 117
Summary and Conclusions 120
References 123
Nutritional and Lifestyle Factors and High-Density Lipoprotein Metabolism 125
Introduction 125
Effects of Dietary Cholesterol 125
Effects of Dietary Fatty Acids 128
Effects of Dietary Carbohydrates 129
Effects of Diets Restricted in Cholesterol and Saturated Fat 129
Effects of Weight Loss 130
Effects of Exercise 130
Conclusions 130
References 131
Effects of Ethanol Intake on High Density Lipoprotein Metabolism in Humans 132
Introduction 132
Effects of Ethanol Dose, Pattern of Intake, and Beverage Type 132
Effects of Ethanol Intake on the Composition and Concentration of Plasma HDL 133
HDL Size Subfractions 133
HDL Lipid Content 134
HDL-Related Apolipoprotein Levels 134
HDL Subfractions by Apolipoprotein Content 134
Mechanisms of HDL Increases with Ethanol: Apolipoprotein Turnover 134
Mechanisms of HDL Increases with Ethanol: Enzymes and Factors Important in HDL Metabolism and Function 135
Effects of Ethanol on Key Aspects of the Protective Effect of HDL Against Atherosclerosis 136
Evidence for Genetic Modulation of HDL Response to Ethanol Intake 137
Summary and Conclusions 138
References 138
Effects of Estrogen on HDL Metabolism 142
References 145
Effects of Niacin on HDL Metabolism 147
References 150
Effects of Statins on HDL Metabolism 152
References 155
Therapeutic Regulation of High-Density Lipoprotein Transport in the Metabolic Syndrome 157
Introduction 157
Principles of Tracer Methods 157
HDL Tracer Kinetics in Metabolic Syndrome 158
Intervention Studies on HDL Kinetics in Metabolic Syndrome 160
Weight Loss 160
Fish Oil Supplementation 160
Peroxisome Proliferator-Activated Receptor-a Agonists 161
Statins 161
Conclusions 161
References 162
Effects of Cholesterol Ester Transfer Protein Inhibition on HDL Metabolism 164
Introduction 164
CETP Genetic Variation and CHD Risk 164
The Development of CETP Inhibitors 166
Vaccine 166
Dalcetrapib 166
Torcetrapib 167
Anacetrapib 168
Conclusions 168
References 168
HDL Infusion Therapy 171
ApoA-I Infusions 172
HDL Mimetic Peptides 174
Summary 175
References 175
High Density Lipoproteins, Dyslipidemia, and Heart Disease: Past, Present, and Future 178
Introduction 178
Lipoprotein Assessment 178
Lipoprotein Assessment by Ultracentrifugation 179
Lipoprotein Assessment by Gradient Gel Electrophoresis 180
Lipoprotein Assessment by Nuclear Magnetic Resonance 180
Standard Lipoprotein Assessment Using Precipitation Methods 181
Lipoprotein Assessment by Specialized Precipitation Methods 182
Apolipoproteins 182
Inflammatory Markers 183
Coronary Heart Disease Risk Assessment 184
Framingham Risk Assessment 186
Reynolds Risk Score and PROCAM Risk Prediction 186
The INTERHEART Experience 187
The Polypill 187
Secondary Causes of Lipid Abnormalities 187
Common Genetic Forms of HDL Deficiency 187
Diet and Lifestyle Modification 188
Pharmacologic Agents 188
Statins 188
Fibrates 188
Niacin 189
Ezetimibe 190
Anion Exchange Resins 190
Fish Oil Capsules 190
Therapies Under Development 191
Conclusions 191
References 192
Index 197

Produkt-Details

• Erscheint lt. Verlag: 10.3.2010
• Zusatzinfo: XI, 205 p. 125 illus., 96 illus. in color.
• Verlagsort: New York
• Sprache: englisch
• Themenwelt: Medizin / Pharmazie ► Gesundheitswesen
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Allgemeinmedizin
• Themenwelt: Medizinische Fachgebiete ► Innere Medizin ► Kardiologie / Angiologie
• Schlagworte: apolipoprotein • atherosclerosis • Cholesterol • coronary heart disease • Diagnosis • Dyslipidemia • Genetics • HDL • heart • high-density lipoprotein (HDL) • Infusion • Lipids • lipoprotein • Nutrition • therapy
• ISBN-10: 1-4419-1059-X / 144191059X
• ISBN-13: 978-1-4419-1059-2 / 9781441910592