Anatol Kontush, M. John Chapman
High-Density Lipoproteins
Structure, Metabolism, Function and Therapeutics
Anatol Kontush, M. John Chapman
High-Density Lipoproteins
Structure, Metabolism, Function and Therapeutics
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A complete guide to the role of high-density lipoproteins (HDL) in new and emerging therapies
With high-density lipoproteins (HDL) playing an increasing role in cardiovascular disease prevention, there is a growing need for an in-depth look at HDL and its clinical value. This book summarizes the current state of knowledge in the field, providing for the first time a comprehensive, systematic, stylistically coherent, and up-to-date review of the composition, structure, heterogeneity, metabolism, epidemiology, genetics, and function of HDL.
Divided into three main parts, High-Density…mehr
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A complete guide to the role of high-density lipoproteins (HDL) in new and emerging therapies
With high-density lipoproteins (HDL) playing an increasing role in cardiovascular disease prevention, there is a growing need for an in-depth look at HDL and its clinical value. This book summarizes the current state of knowledge in the field, providing for the first time a comprehensive, systematic, stylistically coherent, and up-to-date review of the composition, structure, heterogeneity, metabolism, epidemiology, genetics, and function of HDL.
Divided into three main parts, High-Density Lipoproteins first examines normal HDL particles, then describes defective HDL, and finally addresses the therapeutic normalization of subnormal levels and defective biological activities of this lipoprotein class. The book highlights the functional properties of HDL, which are relevant to the pathophysiology of atherosclerosis and thrombosis, and discusses the compositional and metabolic heterogeneity of HDL particles.
Readers will come away with a clear understanding of the role of HDL in biological processes, the potential value of functional HDL as a therapeutic target, and how current and emerging therapies are poised to influence the treatment of heart disease in the future.
Hinweis: Dieser Artikel kann nur an eine deutsche Lieferadresse ausgeliefert werden.
With high-density lipoproteins (HDL) playing an increasing role in cardiovascular disease prevention, there is a growing need for an in-depth look at HDL and its clinical value. This book summarizes the current state of knowledge in the field, providing for the first time a comprehensive, systematic, stylistically coherent, and up-to-date review of the composition, structure, heterogeneity, metabolism, epidemiology, genetics, and function of HDL.
Divided into three main parts, High-Density Lipoproteins first examines normal HDL particles, then describes defective HDL, and finally addresses the therapeutic normalization of subnormal levels and defective biological activities of this lipoprotein class. The book highlights the functional properties of HDL, which are relevant to the pathophysiology of atherosclerosis and thrombosis, and discusses the compositional and metabolic heterogeneity of HDL particles.
Readers will come away with a clear understanding of the role of HDL in biological processes, the potential value of functional HDL as a therapeutic target, and how current and emerging therapies are poised to influence the treatment of heart disease in the future.
Hinweis: Dieser Artikel kann nur an eine deutsche Lieferadresse ausgeliefert werden.
Produktdetails
- Produktdetails
- Verlag: Wiley & Sons
- 1. Auflage
- Seitenzahl: 648
- Erscheinungstermin: 11. Januar 2012
- Englisch
- Abmessung: 240mm x 161mm x 39mm
- Gewicht: 1089g
- ISBN-13: 9780470408216
- ISBN-10: 0470408219
- Artikelnr.: 33870612
- Verlag: Wiley & Sons
- 1. Auflage
- Seitenzahl: 648
- Erscheinungstermin: 11. Januar 2012
- Englisch
- Abmessung: 240mm x 161mm x 39mm
- Gewicht: 1089g
- ISBN-13: 9780470408216
- ISBN-10: 0470408219
- Artikelnr.: 33870612
Anatol Kontush, BSc (Hons), PhD, is Research Director at the Dyslipidemia and Atherosclerosis Research Unit of the National Institute of Health and Medical Research (INSERM) at the Pitié-Salpêtrière Hospital, Paris, France. An award-winning scientist, Dr. Kontush has authored more than 100 original papers and book chapters. M. John Chapman, BSc, PhD, DSc, FESC, is President of the European Atherosclerosis Society and Director of the Dyslipidemia and Atherosclerosis Research Unit of the National Institute of Health and Medical Research (INSERM) at the Pitié-Salpêtrière Hospital in Paris, France, affiliated with the medical faculty of the Pierre and Marie Curie University, Paris. He has authored more than 400 articles and book chapters.
PREFACE xv ACKNOWLEDGMENTS xxxi ABBREVIATIONS xxxiii SECTION 1 NORMAL FUNCTIONAL HIGH-DENSITY LIPOPROTEIN 1 1 COMPOSITION 3 1.1 Proteome
9 Apolipoproteins
9 Apolipoprotein A-I
9 ApoA-II
9 ApoA-IV
9 ApoA-V
10 ApoC-I, ApoC-II, ApoC-III, ApoC-IV
12 ApoD
12 ApoE
13 ApoF
14 ApoH
14 ApoJ
14 ApoL-I
15 ApoM
15 Other Apolipoproteins
15 Enzymes
16 LCAT
16 PON1 and PON3
16 PAF-AH (LpPLA2)
17 GSPx-3
18 Lipid Transfer Proteins
18 PLTP
18 CETP
19 Acute-Phase Response Proteins
19 Serum Amyloid A
19 Other Proteins
20 Complement Components
21 Proteinase Inhibitors and Related Proteins
23 Other Protein Components
25 1.2 Lipidome
27 Phospholipids
27 Steroids
28 Cholesteryl Esters
28 Triglycerides
28 Minor Lipids
28 2 HETEROGENEITY 39 2.1 Heterogeneity in Physicochemical Properties
42 Heterogeneity in Density
42 Heterogeneity in Electrophoretic Mobility
43 Heterogeneity in Size
45 2.2 Heterogeneity in Chemical Composition
47 Heterogeneity in Proteins
47 Heterogeneity in Lipids
49 2.3 Relationships Between HDL Subfractions Separated by Different Methods
50 3 STRUCTURE 59 3.1 Lipid-Free ApoA-I
59 3.2 Discoid HDL
62 3.3 Spherical HDL
66 4 METABOLISM 74 4.1 Formation and Intravascular Remodeling
74 ABC Transporters
77 ABCA1
77 ABCG1
85 Enzymes
86 LCAT
86 Lipases
88 Lipid Transfer Proteins
90 CETP
90 PLTP
92 Receptors
93 SR-BI
93 4.2 Catabolism
96 5 EPIDEMIOLOGY 113 5.1 Epidemiology of HDL-C
113 HDL-C and Cardiovascular Risk
113 Relevance Across Multiple Populations and Disease States
116 HDL-C and Other Cardiovascular Risk Factors
120 Prevalence of Low HDL-C
122 HDL-C and Cardiovascular Risk in Patients Receiving Statins
123 HDL-C and Other Major Diseases
125 5.2 Epidemiology of HDL-Associated Proteins and Enzymes
126 ApoA-I
126 Other Apolipoproteins
129 SAA
130 PON1
130 PAF-AH
131 Other Enzymes
133 Lipid Transfer Proteins
133 5.3 Epidemiology of HDL Particle Subpopulations
134 Separated by Density
134 Separated by Electrophoretic Mobility
135 Separated by Composition
135 Separated by Size
135 6 GENETICS 161 6.1 ABC Transporters and Other Receptors
165 ABCA1
165 SR-BI
167 LDL Receptor
167 6.2 Apolipoproteins
167 ApoA-I
167 ApoA-V
168 ApoC-III
168 ApoE
168 6.3 Enzymes
169 LCAT
169 PON1
169 LPL
170 Hepatic Lipase
171 Endothelial Lipase
171 6.4 Lipid Transfer Proteins
172 CETP
172 6.5 Other Genes
174 6.6 Gene Interactions
176 7 BIOLOGIC ACTIVITIES 192 7.1 Cholesterol Efflux Capacity
197 Mechanisms of Cellular Cholesterol Efflux
199 ABCA1-Mediated Efflux
199 ABCG1-Mediated Efflux
203 SR-BI-Mediated Efflux
204 Other Pathways
205 Role of HDL Components
206 Proteins
206 Lipids
208 Functional Heterogeneity of HDL
210 7.2 Antioxidative Activity
213 Mechanisms of Protection Against Oxidative Stress
216 Role of HDL Components
219 Apolipoproteins
219 Enzymes
220 Lipids
223 Functional Heterogeneity of HDL
224 7.3 Anti-Inflammatory Activity
226 Mechanisms of Anti-Inflammatory Protection
231 Role of HDL Components
234 Proteome
234 Lipidome
235 Functional Heterogeneity of HDL
236 7.4 Cytoprotective Activity
236 Mechanisms of Cytoprotection
238 Role of HDL Components
241 Proteome
241 Lipidome
241 Functional Heterogeneity of HDL
242 7.5 Anti-Infectious Activity
243 Mechanisms of Protection from Infection
245 Role of HDL Components
246 Proteome
246 Lipids
248 Functional Heterogeneity of HDL
248 7.6 Vasodilatory Activity
249 Mechanisms of Vasodilatory Activity
250 Role of HDL Components
252 Proteins
252 Lipids
252 Functional Heterogeneity of HDL
253 7.7 Antithrombotic Activity
253 Mechanisms of Antithrombotic Effects
256 Role of HDL Components
257 Functional Heterogeneity of HDL
258 7.8 Antidiabetic Activity
259 SECTION 2 FUNCTIONALLY DEFECTIVE HDL 305 8 ALTERED COMPOSITION 307 8.1 Proteome
307 8.2 Lipidome
311 8.3 Enzymatic Activities
313 9 ABNORMAL METABOLISM 329 9.1 Dyslipidemias
329 9.2 Insulin-Resistant States
337 9.3 Inflammatory States
339 9.4 Infectious Diseases
341 9.5 Cardiovascular Disease
342 9.6 Post-Prandial State
343 9.7 Smoking
344 10 IMPAIRED BIOLOGIC ACTIVITIES 360 10.1 Cholesterol Efflux Capacity
361 Dyslipidemia
361 Role of HDL Components
364 Insulin Resistance
365 Role of HDL Components
367 Inflammation
369 Cardiovascular Disease
372 Pathophysiologic Relevance
373 10.2 Antioxidative Activity
373 Dyslipidemia
373 Role of HDL Components
374 Insulin Resistance
376 Role of HDL Components
376 Inflammation
379 Infection
380 Cardiovascular Disease
380 Pathophysiologic Relevance
381 10.3 Anti-Inflammatory Activity
382 Dyslipidemia
382 Insulin Resistance
385 Inflammation
386 Cardiovascular Disease
388 Pathophysiologic Relevance
389 10.4 Cytoprotective Activity
391 10.5 Vasodilatory Activity
392 10.6 Anti-Infectious Activity
394 10.7 Antithrombotic Activity
395 SECTION 3 THERAPEUTIC NORMALIZATION OF SUBNORMAL LEVELS AND DEFECTIVE BIOLOGIC ACTIVITIES OF HDL 417 11 ENHANCEMENT OF HDL FORMATION AND NORMALIZATION OF INTRAVASCULAR HDL REMODELING 423 11.1 Apolipoproteins
423 11.2 Reconstituted HDL
428 Effects on HDL Levels and Metabolism
428 Effects on HDL Functionality
430 Role of HDL Components
432 11.3 Apolipoprotein-Mimetic Peptides
434 Effects on HDL Levels and Metabolism
434 Effects on HDL Functionality
434 11.4 Statins
440 Effects on HDL Levels and Metabolism
440 Effects on HDL Functionality
444 Clinical Trials
446 11.5 PPAR Alpha Agonists
447 Effects on HDL Levels
447 Mechanisms of Action
448 Effects on HDL Functionality
451 Clinical Trials
452 11.6 Nicotinic Acid
454 Mechanisms of Action
455 Clinical Trials
458 Effects on HDL Functionality
460 Adverse Effects
461 11.7 CETP Inhibitors
463 Torcetrapib
464 Dalcetrapib
467 Anacetrapib
467 Effects on RCT
469 Clinical Trials
471 Effects on HDL Functionality
474 11.8 Other Agents
477 LXR Agonists
477 PPAR Gamma Agonists
478 Lipase Inhibitors
479 sPLA2 Inhibitors
480 Endothelial Lipase Inhibitors
481 LpPLA2 Inhibitors
481 SR-BI Inhibitors
482 Others
483 12 COMBINATION THERAPIES 524 12.1 Niacin and Statins
524 12.2 Fibrates and Statins
527 12.3 Other Combinations
528 13 OTHER PHARMACOLOGIC APPROACHES 533 13.1 Cannabinoid Type 1 Receptor Antagonists
533 13.2 Estrogens
536 13.3 Others
538 14 LIFESTYLE MODIFICATIONS 542 14.1 Exercise
542 14.2 Alcohol
546 14.3 Nutritional Factors
548 Dietary Fats
548 Cholesterol
548 Phospholipids
549 Saturated Fatty Acids
549 Monounsaturated Fatty Acids
550 PUFAs
550 Carbohydrates
552 Proteins
553 Minor Dietary Components
554 Polyphenols
554 Vitamins
556 Other Minor Components
556 CONCLUSIONS AND PERSPECTIVES 572 INDEX 577
9 Apolipoproteins
9 Apolipoprotein A-I
9 ApoA-II
9 ApoA-IV
9 ApoA-V
10 ApoC-I, ApoC-II, ApoC-III, ApoC-IV
12 ApoD
12 ApoE
13 ApoF
14 ApoH
14 ApoJ
14 ApoL-I
15 ApoM
15 Other Apolipoproteins
15 Enzymes
16 LCAT
16 PON1 and PON3
16 PAF-AH (LpPLA2)
17 GSPx-3
18 Lipid Transfer Proteins
18 PLTP
18 CETP
19 Acute-Phase Response Proteins
19 Serum Amyloid A
19 Other Proteins
20 Complement Components
21 Proteinase Inhibitors and Related Proteins
23 Other Protein Components
25 1.2 Lipidome
27 Phospholipids
27 Steroids
28 Cholesteryl Esters
28 Triglycerides
28 Minor Lipids
28 2 HETEROGENEITY 39 2.1 Heterogeneity in Physicochemical Properties
42 Heterogeneity in Density
42 Heterogeneity in Electrophoretic Mobility
43 Heterogeneity in Size
45 2.2 Heterogeneity in Chemical Composition
47 Heterogeneity in Proteins
47 Heterogeneity in Lipids
49 2.3 Relationships Between HDL Subfractions Separated by Different Methods
50 3 STRUCTURE 59 3.1 Lipid-Free ApoA-I
59 3.2 Discoid HDL
62 3.3 Spherical HDL
66 4 METABOLISM 74 4.1 Formation and Intravascular Remodeling
74 ABC Transporters
77 ABCA1
77 ABCG1
85 Enzymes
86 LCAT
86 Lipases
88 Lipid Transfer Proteins
90 CETP
90 PLTP
92 Receptors
93 SR-BI
93 4.2 Catabolism
96 5 EPIDEMIOLOGY 113 5.1 Epidemiology of HDL-C
113 HDL-C and Cardiovascular Risk
113 Relevance Across Multiple Populations and Disease States
116 HDL-C and Other Cardiovascular Risk Factors
120 Prevalence of Low HDL-C
122 HDL-C and Cardiovascular Risk in Patients Receiving Statins
123 HDL-C and Other Major Diseases
125 5.2 Epidemiology of HDL-Associated Proteins and Enzymes
126 ApoA-I
126 Other Apolipoproteins
129 SAA
130 PON1
130 PAF-AH
131 Other Enzymes
133 Lipid Transfer Proteins
133 5.3 Epidemiology of HDL Particle Subpopulations
134 Separated by Density
134 Separated by Electrophoretic Mobility
135 Separated by Composition
135 Separated by Size
135 6 GENETICS 161 6.1 ABC Transporters and Other Receptors
165 ABCA1
165 SR-BI
167 LDL Receptor
167 6.2 Apolipoproteins
167 ApoA-I
167 ApoA-V
168 ApoC-III
168 ApoE
168 6.3 Enzymes
169 LCAT
169 PON1
169 LPL
170 Hepatic Lipase
171 Endothelial Lipase
171 6.4 Lipid Transfer Proteins
172 CETP
172 6.5 Other Genes
174 6.6 Gene Interactions
176 7 BIOLOGIC ACTIVITIES 192 7.1 Cholesterol Efflux Capacity
197 Mechanisms of Cellular Cholesterol Efflux
199 ABCA1-Mediated Efflux
199 ABCG1-Mediated Efflux
203 SR-BI-Mediated Efflux
204 Other Pathways
205 Role of HDL Components
206 Proteins
206 Lipids
208 Functional Heterogeneity of HDL
210 7.2 Antioxidative Activity
213 Mechanisms of Protection Against Oxidative Stress
216 Role of HDL Components
219 Apolipoproteins
219 Enzymes
220 Lipids
223 Functional Heterogeneity of HDL
224 7.3 Anti-Inflammatory Activity
226 Mechanisms of Anti-Inflammatory Protection
231 Role of HDL Components
234 Proteome
234 Lipidome
235 Functional Heterogeneity of HDL
236 7.4 Cytoprotective Activity
236 Mechanisms of Cytoprotection
238 Role of HDL Components
241 Proteome
241 Lipidome
241 Functional Heterogeneity of HDL
242 7.5 Anti-Infectious Activity
243 Mechanisms of Protection from Infection
245 Role of HDL Components
246 Proteome
246 Lipids
248 Functional Heterogeneity of HDL
248 7.6 Vasodilatory Activity
249 Mechanisms of Vasodilatory Activity
250 Role of HDL Components
252 Proteins
252 Lipids
252 Functional Heterogeneity of HDL
253 7.7 Antithrombotic Activity
253 Mechanisms of Antithrombotic Effects
256 Role of HDL Components
257 Functional Heterogeneity of HDL
258 7.8 Antidiabetic Activity
259 SECTION 2 FUNCTIONALLY DEFECTIVE HDL 305 8 ALTERED COMPOSITION 307 8.1 Proteome
307 8.2 Lipidome
311 8.3 Enzymatic Activities
313 9 ABNORMAL METABOLISM 329 9.1 Dyslipidemias
329 9.2 Insulin-Resistant States
337 9.3 Inflammatory States
339 9.4 Infectious Diseases
341 9.5 Cardiovascular Disease
342 9.6 Post-Prandial State
343 9.7 Smoking
344 10 IMPAIRED BIOLOGIC ACTIVITIES 360 10.1 Cholesterol Efflux Capacity
361 Dyslipidemia
361 Role of HDL Components
364 Insulin Resistance
365 Role of HDL Components
367 Inflammation
369 Cardiovascular Disease
372 Pathophysiologic Relevance
373 10.2 Antioxidative Activity
373 Dyslipidemia
373 Role of HDL Components
374 Insulin Resistance
376 Role of HDL Components
376 Inflammation
379 Infection
380 Cardiovascular Disease
380 Pathophysiologic Relevance
381 10.3 Anti-Inflammatory Activity
382 Dyslipidemia
382 Insulin Resistance
385 Inflammation
386 Cardiovascular Disease
388 Pathophysiologic Relevance
389 10.4 Cytoprotective Activity
391 10.5 Vasodilatory Activity
392 10.6 Anti-Infectious Activity
394 10.7 Antithrombotic Activity
395 SECTION 3 THERAPEUTIC NORMALIZATION OF SUBNORMAL LEVELS AND DEFECTIVE BIOLOGIC ACTIVITIES OF HDL 417 11 ENHANCEMENT OF HDL FORMATION AND NORMALIZATION OF INTRAVASCULAR HDL REMODELING 423 11.1 Apolipoproteins
423 11.2 Reconstituted HDL
428 Effects on HDL Levels and Metabolism
428 Effects on HDL Functionality
430 Role of HDL Components
432 11.3 Apolipoprotein-Mimetic Peptides
434 Effects on HDL Levels and Metabolism
434 Effects on HDL Functionality
434 11.4 Statins
440 Effects on HDL Levels and Metabolism
440 Effects on HDL Functionality
444 Clinical Trials
446 11.5 PPAR Alpha Agonists
447 Effects on HDL Levels
447 Mechanisms of Action
448 Effects on HDL Functionality
451 Clinical Trials
452 11.6 Nicotinic Acid
454 Mechanisms of Action
455 Clinical Trials
458 Effects on HDL Functionality
460 Adverse Effects
461 11.7 CETP Inhibitors
463 Torcetrapib
464 Dalcetrapib
467 Anacetrapib
467 Effects on RCT
469 Clinical Trials
471 Effects on HDL Functionality
474 11.8 Other Agents
477 LXR Agonists
477 PPAR Gamma Agonists
478 Lipase Inhibitors
479 sPLA2 Inhibitors
480 Endothelial Lipase Inhibitors
481 LpPLA2 Inhibitors
481 SR-BI Inhibitors
482 Others
483 12 COMBINATION THERAPIES 524 12.1 Niacin and Statins
524 12.2 Fibrates and Statins
527 12.3 Other Combinations
528 13 OTHER PHARMACOLOGIC APPROACHES 533 13.1 Cannabinoid Type 1 Receptor Antagonists
533 13.2 Estrogens
536 13.3 Others
538 14 LIFESTYLE MODIFICATIONS 542 14.1 Exercise
542 14.2 Alcohol
546 14.3 Nutritional Factors
548 Dietary Fats
548 Cholesterol
548 Phospholipids
549 Saturated Fatty Acids
549 Monounsaturated Fatty Acids
550 PUFAs
550 Carbohydrates
552 Proteins
553 Minor Dietary Components
554 Polyphenols
554 Vitamins
556 Other Minor Components
556 CONCLUSIONS AND PERSPECTIVES 572 INDEX 577
PREFACE xv ACKNOWLEDGMENTS xxxi ABBREVIATIONS xxxiii SECTION 1 NORMAL FUNCTIONAL HIGH-DENSITY LIPOPROTEIN 1 1 COMPOSITION 3 1.1 Proteome
9 Apolipoproteins
9 Apolipoprotein A-I
9 ApoA-II
9 ApoA-IV
9 ApoA-V
10 ApoC-I, ApoC-II, ApoC-III, ApoC-IV
12 ApoD
12 ApoE
13 ApoF
14 ApoH
14 ApoJ
14 ApoL-I
15 ApoM
15 Other Apolipoproteins
15 Enzymes
16 LCAT
16 PON1 and PON3
16 PAF-AH (LpPLA2)
17 GSPx-3
18 Lipid Transfer Proteins
18 PLTP
18 CETP
19 Acute-Phase Response Proteins
19 Serum Amyloid A
19 Other Proteins
20 Complement Components
21 Proteinase Inhibitors and Related Proteins
23 Other Protein Components
25 1.2 Lipidome
27 Phospholipids
27 Steroids
28 Cholesteryl Esters
28 Triglycerides
28 Minor Lipids
28 2 HETEROGENEITY 39 2.1 Heterogeneity in Physicochemical Properties
42 Heterogeneity in Density
42 Heterogeneity in Electrophoretic Mobility
43 Heterogeneity in Size
45 2.2 Heterogeneity in Chemical Composition
47 Heterogeneity in Proteins
47 Heterogeneity in Lipids
49 2.3 Relationships Between HDL Subfractions Separated by Different Methods
50 3 STRUCTURE 59 3.1 Lipid-Free ApoA-I
59 3.2 Discoid HDL
62 3.3 Spherical HDL
66 4 METABOLISM 74 4.1 Formation and Intravascular Remodeling
74 ABC Transporters
77 ABCA1
77 ABCG1
85 Enzymes
86 LCAT
86 Lipases
88 Lipid Transfer Proteins
90 CETP
90 PLTP
92 Receptors
93 SR-BI
93 4.2 Catabolism
96 5 EPIDEMIOLOGY 113 5.1 Epidemiology of HDL-C
113 HDL-C and Cardiovascular Risk
113 Relevance Across Multiple Populations and Disease States
116 HDL-C and Other Cardiovascular Risk Factors
120 Prevalence of Low HDL-C
122 HDL-C and Cardiovascular Risk in Patients Receiving Statins
123 HDL-C and Other Major Diseases
125 5.2 Epidemiology of HDL-Associated Proteins and Enzymes
126 ApoA-I
126 Other Apolipoproteins
129 SAA
130 PON1
130 PAF-AH
131 Other Enzymes
133 Lipid Transfer Proteins
133 5.3 Epidemiology of HDL Particle Subpopulations
134 Separated by Density
134 Separated by Electrophoretic Mobility
135 Separated by Composition
135 Separated by Size
135 6 GENETICS 161 6.1 ABC Transporters and Other Receptors
165 ABCA1
165 SR-BI
167 LDL Receptor
167 6.2 Apolipoproteins
167 ApoA-I
167 ApoA-V
168 ApoC-III
168 ApoE
168 6.3 Enzymes
169 LCAT
169 PON1
169 LPL
170 Hepatic Lipase
171 Endothelial Lipase
171 6.4 Lipid Transfer Proteins
172 CETP
172 6.5 Other Genes
174 6.6 Gene Interactions
176 7 BIOLOGIC ACTIVITIES 192 7.1 Cholesterol Efflux Capacity
197 Mechanisms of Cellular Cholesterol Efflux
199 ABCA1-Mediated Efflux
199 ABCG1-Mediated Efflux
203 SR-BI-Mediated Efflux
204 Other Pathways
205 Role of HDL Components
206 Proteins
206 Lipids
208 Functional Heterogeneity of HDL
210 7.2 Antioxidative Activity
213 Mechanisms of Protection Against Oxidative Stress
216 Role of HDL Components
219 Apolipoproteins
219 Enzymes
220 Lipids
223 Functional Heterogeneity of HDL
224 7.3 Anti-Inflammatory Activity
226 Mechanisms of Anti-Inflammatory Protection
231 Role of HDL Components
234 Proteome
234 Lipidome
235 Functional Heterogeneity of HDL
236 7.4 Cytoprotective Activity
236 Mechanisms of Cytoprotection
238 Role of HDL Components
241 Proteome
241 Lipidome
241 Functional Heterogeneity of HDL
242 7.5 Anti-Infectious Activity
243 Mechanisms of Protection from Infection
245 Role of HDL Components
246 Proteome
246 Lipids
248 Functional Heterogeneity of HDL
248 7.6 Vasodilatory Activity
249 Mechanisms of Vasodilatory Activity
250 Role of HDL Components
252 Proteins
252 Lipids
252 Functional Heterogeneity of HDL
253 7.7 Antithrombotic Activity
253 Mechanisms of Antithrombotic Effects
256 Role of HDL Components
257 Functional Heterogeneity of HDL
258 7.8 Antidiabetic Activity
259 SECTION 2 FUNCTIONALLY DEFECTIVE HDL 305 8 ALTERED COMPOSITION 307 8.1 Proteome
307 8.2 Lipidome
311 8.3 Enzymatic Activities
313 9 ABNORMAL METABOLISM 329 9.1 Dyslipidemias
329 9.2 Insulin-Resistant States
337 9.3 Inflammatory States
339 9.4 Infectious Diseases
341 9.5 Cardiovascular Disease
342 9.6 Post-Prandial State
343 9.7 Smoking
344 10 IMPAIRED BIOLOGIC ACTIVITIES 360 10.1 Cholesterol Efflux Capacity
361 Dyslipidemia
361 Role of HDL Components
364 Insulin Resistance
365 Role of HDL Components
367 Inflammation
369 Cardiovascular Disease
372 Pathophysiologic Relevance
373 10.2 Antioxidative Activity
373 Dyslipidemia
373 Role of HDL Components
374 Insulin Resistance
376 Role of HDL Components
376 Inflammation
379 Infection
380 Cardiovascular Disease
380 Pathophysiologic Relevance
381 10.3 Anti-Inflammatory Activity
382 Dyslipidemia
382 Insulin Resistance
385 Inflammation
386 Cardiovascular Disease
388 Pathophysiologic Relevance
389 10.4 Cytoprotective Activity
391 10.5 Vasodilatory Activity
392 10.6 Anti-Infectious Activity
394 10.7 Antithrombotic Activity
395 SECTION 3 THERAPEUTIC NORMALIZATION OF SUBNORMAL LEVELS AND DEFECTIVE BIOLOGIC ACTIVITIES OF HDL 417 11 ENHANCEMENT OF HDL FORMATION AND NORMALIZATION OF INTRAVASCULAR HDL REMODELING 423 11.1 Apolipoproteins
423 11.2 Reconstituted HDL
428 Effects on HDL Levels and Metabolism
428 Effects on HDL Functionality
430 Role of HDL Components
432 11.3 Apolipoprotein-Mimetic Peptides
434 Effects on HDL Levels and Metabolism
434 Effects on HDL Functionality
434 11.4 Statins
440 Effects on HDL Levels and Metabolism
440 Effects on HDL Functionality
444 Clinical Trials
446 11.5 PPAR Alpha Agonists
447 Effects on HDL Levels
447 Mechanisms of Action
448 Effects on HDL Functionality
451 Clinical Trials
452 11.6 Nicotinic Acid
454 Mechanisms of Action
455 Clinical Trials
458 Effects on HDL Functionality
460 Adverse Effects
461 11.7 CETP Inhibitors
463 Torcetrapib
464 Dalcetrapib
467 Anacetrapib
467 Effects on RCT
469 Clinical Trials
471 Effects on HDL Functionality
474 11.8 Other Agents
477 LXR Agonists
477 PPAR Gamma Agonists
478 Lipase Inhibitors
479 sPLA2 Inhibitors
480 Endothelial Lipase Inhibitors
481 LpPLA2 Inhibitors
481 SR-BI Inhibitors
482 Others
483 12 COMBINATION THERAPIES 524 12.1 Niacin and Statins
524 12.2 Fibrates and Statins
527 12.3 Other Combinations
528 13 OTHER PHARMACOLOGIC APPROACHES 533 13.1 Cannabinoid Type 1 Receptor Antagonists
533 13.2 Estrogens
536 13.3 Others
538 14 LIFESTYLE MODIFICATIONS 542 14.1 Exercise
542 14.2 Alcohol
546 14.3 Nutritional Factors
548 Dietary Fats
548 Cholesterol
548 Phospholipids
549 Saturated Fatty Acids
549 Monounsaturated Fatty Acids
550 PUFAs
550 Carbohydrates
552 Proteins
553 Minor Dietary Components
554 Polyphenols
554 Vitamins
556 Other Minor Components
556 CONCLUSIONS AND PERSPECTIVES 572 INDEX 577
9 Apolipoproteins
9 Apolipoprotein A-I
9 ApoA-II
9 ApoA-IV
9 ApoA-V
10 ApoC-I, ApoC-II, ApoC-III, ApoC-IV
12 ApoD
12 ApoE
13 ApoF
14 ApoH
14 ApoJ
14 ApoL-I
15 ApoM
15 Other Apolipoproteins
15 Enzymes
16 LCAT
16 PON1 and PON3
16 PAF-AH (LpPLA2)
17 GSPx-3
18 Lipid Transfer Proteins
18 PLTP
18 CETP
19 Acute-Phase Response Proteins
19 Serum Amyloid A
19 Other Proteins
20 Complement Components
21 Proteinase Inhibitors and Related Proteins
23 Other Protein Components
25 1.2 Lipidome
27 Phospholipids
27 Steroids
28 Cholesteryl Esters
28 Triglycerides
28 Minor Lipids
28 2 HETEROGENEITY 39 2.1 Heterogeneity in Physicochemical Properties
42 Heterogeneity in Density
42 Heterogeneity in Electrophoretic Mobility
43 Heterogeneity in Size
45 2.2 Heterogeneity in Chemical Composition
47 Heterogeneity in Proteins
47 Heterogeneity in Lipids
49 2.3 Relationships Between HDL Subfractions Separated by Different Methods
50 3 STRUCTURE 59 3.1 Lipid-Free ApoA-I
59 3.2 Discoid HDL
62 3.3 Spherical HDL
66 4 METABOLISM 74 4.1 Formation and Intravascular Remodeling
74 ABC Transporters
77 ABCA1
77 ABCG1
85 Enzymes
86 LCAT
86 Lipases
88 Lipid Transfer Proteins
90 CETP
90 PLTP
92 Receptors
93 SR-BI
93 4.2 Catabolism
96 5 EPIDEMIOLOGY 113 5.1 Epidemiology of HDL-C
113 HDL-C and Cardiovascular Risk
113 Relevance Across Multiple Populations and Disease States
116 HDL-C and Other Cardiovascular Risk Factors
120 Prevalence of Low HDL-C
122 HDL-C and Cardiovascular Risk in Patients Receiving Statins
123 HDL-C and Other Major Diseases
125 5.2 Epidemiology of HDL-Associated Proteins and Enzymes
126 ApoA-I
126 Other Apolipoproteins
129 SAA
130 PON1
130 PAF-AH
131 Other Enzymes
133 Lipid Transfer Proteins
133 5.3 Epidemiology of HDL Particle Subpopulations
134 Separated by Density
134 Separated by Electrophoretic Mobility
135 Separated by Composition
135 Separated by Size
135 6 GENETICS 161 6.1 ABC Transporters and Other Receptors
165 ABCA1
165 SR-BI
167 LDL Receptor
167 6.2 Apolipoproteins
167 ApoA-I
167 ApoA-V
168 ApoC-III
168 ApoE
168 6.3 Enzymes
169 LCAT
169 PON1
169 LPL
170 Hepatic Lipase
171 Endothelial Lipase
171 6.4 Lipid Transfer Proteins
172 CETP
172 6.5 Other Genes
174 6.6 Gene Interactions
176 7 BIOLOGIC ACTIVITIES 192 7.1 Cholesterol Efflux Capacity
197 Mechanisms of Cellular Cholesterol Efflux
199 ABCA1-Mediated Efflux
199 ABCG1-Mediated Efflux
203 SR-BI-Mediated Efflux
204 Other Pathways
205 Role of HDL Components
206 Proteins
206 Lipids
208 Functional Heterogeneity of HDL
210 7.2 Antioxidative Activity
213 Mechanisms of Protection Against Oxidative Stress
216 Role of HDL Components
219 Apolipoproteins
219 Enzymes
220 Lipids
223 Functional Heterogeneity of HDL
224 7.3 Anti-Inflammatory Activity
226 Mechanisms of Anti-Inflammatory Protection
231 Role of HDL Components
234 Proteome
234 Lipidome
235 Functional Heterogeneity of HDL
236 7.4 Cytoprotective Activity
236 Mechanisms of Cytoprotection
238 Role of HDL Components
241 Proteome
241 Lipidome
241 Functional Heterogeneity of HDL
242 7.5 Anti-Infectious Activity
243 Mechanisms of Protection from Infection
245 Role of HDL Components
246 Proteome
246 Lipids
248 Functional Heterogeneity of HDL
248 7.6 Vasodilatory Activity
249 Mechanisms of Vasodilatory Activity
250 Role of HDL Components
252 Proteins
252 Lipids
252 Functional Heterogeneity of HDL
253 7.7 Antithrombotic Activity
253 Mechanisms of Antithrombotic Effects
256 Role of HDL Components
257 Functional Heterogeneity of HDL
258 7.8 Antidiabetic Activity
259 SECTION 2 FUNCTIONALLY DEFECTIVE HDL 305 8 ALTERED COMPOSITION 307 8.1 Proteome
307 8.2 Lipidome
311 8.3 Enzymatic Activities
313 9 ABNORMAL METABOLISM 329 9.1 Dyslipidemias
329 9.2 Insulin-Resistant States
337 9.3 Inflammatory States
339 9.4 Infectious Diseases
341 9.5 Cardiovascular Disease
342 9.6 Post-Prandial State
343 9.7 Smoking
344 10 IMPAIRED BIOLOGIC ACTIVITIES 360 10.1 Cholesterol Efflux Capacity
361 Dyslipidemia
361 Role of HDL Components
364 Insulin Resistance
365 Role of HDL Components
367 Inflammation
369 Cardiovascular Disease
372 Pathophysiologic Relevance
373 10.2 Antioxidative Activity
373 Dyslipidemia
373 Role of HDL Components
374 Insulin Resistance
376 Role of HDL Components
376 Inflammation
379 Infection
380 Cardiovascular Disease
380 Pathophysiologic Relevance
381 10.3 Anti-Inflammatory Activity
382 Dyslipidemia
382 Insulin Resistance
385 Inflammation
386 Cardiovascular Disease
388 Pathophysiologic Relevance
389 10.4 Cytoprotective Activity
391 10.5 Vasodilatory Activity
392 10.6 Anti-Infectious Activity
394 10.7 Antithrombotic Activity
395 SECTION 3 THERAPEUTIC NORMALIZATION OF SUBNORMAL LEVELS AND DEFECTIVE BIOLOGIC ACTIVITIES OF HDL 417 11 ENHANCEMENT OF HDL FORMATION AND NORMALIZATION OF INTRAVASCULAR HDL REMODELING 423 11.1 Apolipoproteins
423 11.2 Reconstituted HDL
428 Effects on HDL Levels and Metabolism
428 Effects on HDL Functionality
430 Role of HDL Components
432 11.3 Apolipoprotein-Mimetic Peptides
434 Effects on HDL Levels and Metabolism
434 Effects on HDL Functionality
434 11.4 Statins
440 Effects on HDL Levels and Metabolism
440 Effects on HDL Functionality
444 Clinical Trials
446 11.5 PPAR Alpha Agonists
447 Effects on HDL Levels
447 Mechanisms of Action
448 Effects on HDL Functionality
451 Clinical Trials
452 11.6 Nicotinic Acid
454 Mechanisms of Action
455 Clinical Trials
458 Effects on HDL Functionality
460 Adverse Effects
461 11.7 CETP Inhibitors
463 Torcetrapib
464 Dalcetrapib
467 Anacetrapib
467 Effects on RCT
469 Clinical Trials
471 Effects on HDL Functionality
474 11.8 Other Agents
477 LXR Agonists
477 PPAR Gamma Agonists
478 Lipase Inhibitors
479 sPLA2 Inhibitors
480 Endothelial Lipase Inhibitors
481 LpPLA2 Inhibitors
481 SR-BI Inhibitors
482 Others
483 12 COMBINATION THERAPIES 524 12.1 Niacin and Statins
524 12.2 Fibrates and Statins
527 12.3 Other Combinations
528 13 OTHER PHARMACOLOGIC APPROACHES 533 13.1 Cannabinoid Type 1 Receptor Antagonists
533 13.2 Estrogens
536 13.3 Others
538 14 LIFESTYLE MODIFICATIONS 542 14.1 Exercise
542 14.2 Alcohol
546 14.3 Nutritional Factors
548 Dietary Fats
548 Cholesterol
548 Phospholipids
549 Saturated Fatty Acids
549 Monounsaturated Fatty Acids
550 PUFAs
550 Carbohydrates
552 Proteins
553 Minor Dietary Components
554 Polyphenols
554 Vitamins
556 Other Minor Components
556 CONCLUSIONS AND PERSPECTIVES 572 INDEX 577