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High Density Lipoproteins - Arnold von Eckardstein

Year 2015


PrefaceAcknowledgementPart I Physiology of HDL Structure of HDL: Particle Subclasses and Molecular Components1 HDL Subclasses2 Molecular Components of HDL2.1 Proteome2.2 Lipidome3 The Structure of HDL3.1 Introduction/Brief History3.2 HDL in the Test Tube3.3 “Real” HDL ParticlesHDL Biogenesis, Remodeling, and Catabolism1 Biogenesis of HDL1.1 ATP-Binding Cassette Transporter A1 (ABCA1)1.2 Lecithin/Cholesterol Acyltransferase (LCAT)1.3 ApoA-I Mutations May Induce Hypertriglyceridemia and/or Hypercholesterolemia1.4 ApoE and apoA-IV Participate in the Biogenesis of HDL Particles Containing the Corresponding Proteins1.5 Clinical Relevance of the Aberrant HDL Phenotypes2 Remodeling and Catabolism of HDL2.1 ATP-Binding Cassette Transporter G12.2 Phospholipid Transfer Protein2.3 apoM2.4 Hepatic Lipase and Endothelial Lipase2.5 Cholesteryl Ester Transfer Protein2.6 Scavenger Receptor BI2.7 Role of Ecto-F1-ATPase/P2Y13 Pathway in Hepatic HDL Clearance2.8 Transcytosis of apoA-I and HDL by Endothelial Cells2.9 The Role of Cubilin in apoA-I and HDL Catabolism by the Kidney3 HDL Subclasses3.1 The Origin and Metabolism of Preb-HDL Subpopulations3.2 Complexity of HDL4 Sources of FundingRegulation of HDL Genes: Transcriptional, Posttranscriptional, and Posttranslational1 Regulation of Genes Involved in HDL Metabolism at the Transcriptional Level1.1 General Introduction to Hormone Nuclear Receptors1.2 Transcriptional Regulation of the apoA-I Gene in the Liver1.3 Transcriptional Regulation of the ABCA1 Gene1.4 Transcriptional Regulation of the ABCG1 Gene1.5 Transcriptional Regulation of the Apolipoprotein E Gene1.6 Transcriptional Regulation of the Human apoM Gene in the Liver1.7 Transcriptional Regulation of the CETP Gene1.8 Transcriptional Regulation of the PLTP Gene1.9 Transcriptional Regulation of the Bile Acid Transporters ABCG5/ABCG81.10 Transcriptional Regulation of the HDL Receptor SR-BI2 Posttranscriptional Regulation of HDL Genes by Noncoding RNAs and microRNAs2.1 miRNAs: Biogenesis and Function2.2 Posttranscriptional Modulation of HDL Metabolism by miRNAs3 Posttranslational Mechanisms of HDL Regulation3.1 ABCA13.2 ABCG13.3 SR-BICholesterol Efflux and Reverse Cholesterol Transport1 Cholesterol Efflux as the First Step of Reverse Cholesterol Transport (RCT)1.1 ABCA1-Mediated Lipid Efflux to Lipid-Poor apoA-I1.2 Cholesterol Efflux to Lipidated HDL2 HDL Quality and Cholesterol Efflux3 RCT in Animal Models3.1 Physiology3.2 Pharmacology4 Serum Cholesterol Efflux Capacity (CEC)Functionality of HDL: Antioxidation and Detoxifying Effects1 High-Density Lipoproteins and Oxidative Stress1.1 High-Density Lipoproteins: Antioxidative Function1.2 Mechanisms of Protection1.3 Heterogeneity of Antioxidant Activity of HDL Particles2 High-Density Lipoproteins, Paraoxonase-12.1 PON1 as an Antioxidant2.2 PON1 and Bacterial Pathogens3 High-Density Lipoproteins, Environmental Pathogens and Toxins3.1 Bacterial Pathogens3.2 Parasites3.3 Hepatitis, Dengue and Other Viruses3.4 Metal Oxides, Carbon Nanotubes and PLGA Nanoparticles3.5 PON1 and Organophosphates3.6 Detoxification of Plasma and External FluidsSignal Transduction by HDL: Agonists, Receptors, and Signaling Cascades1 Introduction2 ApoA-I-Induced Cell Signaling Directly Mediated by ABCA13 ApoA-I-Induced Cell Signaling Indirectly Mediated by b-ATPase and P2Y12/13 ADP Receptor4 ApoA-Iand HDL-Induced Cell Signaling Indirectly Mediated by ABCA1 and/or ABCG15 HDL-Induced Cell Signaling Mediated by SR-BI6 HDL-Induced Cell Signaling Mediated by S1P7 HDL-Induced Cell Signaling: Future Challenges and OpportunitiesPart II Pathology of HDLEpidemiology: Disease Associations1 Protective Role of HDL: Evidence from Epidemiological Studies2 HDL Cholesterol as a Risk Factor for Atherosclerosis and Its Complications3 HDL Cholesterol as a Risk Factor for Other Diseases4 Total HDL-C in Various Populations5 Total HDL-C Modulated by Environmental Factors6 HDL-C in Diseases and Conditions7 High HDL Levels Do Not Add to the Protection8 Effect of HDL on Stroke9 Time Trends in Total HDL-C10 Are There Other Biomarkers than the Total HDL-C?11 HDL Fractions12 HDL Particle Size13 HDL Particle Number14 HDL Lipids15 HDL Apolipoproteins16 HDL Proteomics17 HDL Function18 Pleiotropy19 Future Approaches of Epidemiological StudiesBeyond the Genetics of HDL: Why Is HDL Cholesterol Inversely Related to Cardiovascular Disease?1 General2 Determinants of Plasma HDL Cholesterol Levels2.1 Established Primary Regulators of Plasma HDL Cholesterol2.2 Established Secondary Regulators of Plasma HDL Cholesterol2.3 Missing Heritability3 Novel Insight into HDL Biology3.1 De Novo Synthesis of HDL and HDL Binding3.2 HDL Conversion and RemodelingMouse Models of Disturbed HDL Metabolism1 Introduction2 Apolipoprotein A-I3 ATP-Binding Cassette Transporter A14 ATP-Binding Cassette Transporter G15 Lecithin-Cholesterol Acyltransferase6 Phospholipid Transfer Protein7 Scavenger Receptor BI8 Insights from Intercrossing of the Different Knockout Mice9 Conclusions from the Gene Knockout Mouse Studies10 Cholesterol Ester Transfer Protein Transgenic MiceDysfunctional HDL: From StructureFunction-Relationships to Biomarkers1 Introduction2 HDL and Reverse Cholesterol Transport2.1 Mechanisms Under Physiological Conditions2.2 Alterations of the Cholesterol Efflux Capacity of HDL in Cardiovascular Disease3 Effects of HDL on LDL Oxidation3.1 Mechanisms Under Physiological Conditions3.2 Impairment of the Anti-Oxidative Effects of HDL in Patients After Surgery and With Cardiovascular Disease4 Effects of HDL on Endothelial Nitric Oxide Bioavailability4.1 Mechanisms Under Physiological Conditions4.2 Impaired HDL Capacity to Stimulate NO Production in Patients with Cardiovascular Disease5 Endothelial Anti-Inflammatory Effects of HDL5.1 Mechanisms Under Physiological Conditions5.2 Impaired Endothelial Anti-Inflammatory Effects of HDL in Patients with CAD, Diabetes, or Chronic Kidney Dysfunction6 Effects of HDL on Endothelial Cell Apoptotic Pathways6.1 Mechanisms Under Physiological Conditions6.2 Impairment of the Endothelial Anti-Apoptotic Effects of HDL in Patients with Cardiovascular Disease7 HDL Protein Cargo and Prognostic BiomarkersPart III Possible Indications and Target Mechanisms of HDL TherapyHDL and Atherothrombotic Vascular Disease1 Introduction2 Interactions of HDLs with the Endothelium2.1 Preservation of Endothelial Integrity2.2 Preservation of Endothelial Function3 Anti-inflammatory Effects3.1 Suppression of Myelopoiesis3.2 Suppression of Monocyte Extravasation3.3 Interference with Macrophage Differentiation and Activation4 Effects of HDLs on Vascular Lipid and Lipoprotein Homeostasis4.1 From LDL Retention to Atheroma Formation4.2 Inhibition of LDL Modification by HDLs4.3 Macrophage Cholesterol Efflux and Reverse Cholesterol Transport5 Atherothrombosis5.1 Effects of HDLs on Smooth Muscle Cells5.2 Antithrombotic Effects of HDLs6 Myocardial InjuryHDLs, Diabetes, and Metabolic Syndrome1 Type 2 Diabetes Mellitus and the Metabolic Syndrome2 Low HDL Cholesterol Levels in Diabetes and Metabolic Syndrome2.1 Insulin Resistance, Hypertriglyceridemia, and Decreased HDL Cholesterol Levels2.2 FFAs and Decreased HDL Levels2.3 HDL Metabolism, Subclasses, and Catabolism3 Does HDL Play a Causal Role in the Pathogenesis of Diabetes?3.1 Effects of HDL on Obesity3.2 Effects of HDL on Insulin Sensitivity and Glucose Utilization by Skeletal Muscle3.3 The Beneficial Effects of HDL in Pancreatic Beta CellsHigh-Density Lipoprotein: Structural and Functional Changes Under Uremic Conditions and the Therapeutic Consequences1 Introduction2 Chronic Kidney Disease: Epidemiology and Pathophysiology3 Dyslipidemia, Lipid-Modulating Therapy, and Cardiovascular Risk in CKD Patients3.1 Dyslipidemia in CKD Patients3.2 Lipid-Modulating Therapy in CKD Patients3.3 Protective Effects of HDL on the Kidney4 Structural and Functional Modifications of HDL in CKD Patients4.1 Dysregulation of Proteins in HDL Metabolism4.2 Changes of HDL Apolipoproteins (Modifications and Levels)4.3 Loss of Protective Proteins or Lipids4.4 Increase of Molecules within HDL with a Fatal Function in the Vascular Wall5 Possibility of Functional Restoration of HDL6 Laboratory Tests to Measure HDL FunctionImpact of Systemic Inflammation and Autoimmune Diseases on apoA-I and HDL Plasma Levels and Functions1 Introduction2 HDL/apoA-I Structure and Function3 HDL and apoA-I as Members of the Innate Immune System4 Relationship Between Lipid Raft Modulation and Lymphocyte Function5 Modulation of Spinghosine-1-Phosphate (S1P)/ S1P-Receptor Axis and Lymphocyte Function6 Inflammatory Diseases6.1 Inflammatory Bowel Diseases6.2 Vasculitis6.3 Psoriasis7 Autoimmune Diseases: The Role of Autoantibodies7.1 Systemic Lupus Erythematosus (SLE)7.2 Rheumatoid Arthritis (RA)8 Impact of Anti-inflammatory TreatmentsHDL in Infectious Diseases and Sepsis1 Introduction2 HDL and Bacterial Infections2.1 Interaction of HDL with LPS and Gram-Negative Bacteria2.2 Interaction of HDL with LTA and Gram-Positive Bacteria2.3 HDL and Mycobacteria2.4 General Innate Host Defense Mechanisms Exerted by HDL After Bacterial Infection3 HDL and Parasitic Infections4 HDL and Viral Infections4.1 HIV Infection4.2 HCV InfectionHigh-Density Lipoproteins in Stroke1 Introduction2 Pleiotropic Effects of HDLs3 HDL Potential Effects on the Blood–Brain Barrier3.1 Reconstituted HDLs and HDL Mimetics4 Part 1: Pleiotropic Effects of HDLs—In Vitro and In Vivo Data4.1 HDLs and Nitric Oxide (NO)4.2 HDLs and Sphingosine 1-Phosphate4.3 Antioxidative Stress4.4 Anti-inflammatory and Antiprotease Properties4.5 Endothelial Cell Integrity, EPCs and Antiapoptotic Action4.6 Antithrombotic Actions5 HDLs in the Cerebral Compartment5.1 Lipoproteins in the Brain5.2 Plasma HDLs in the Brain6 Part 2: HDLs and Acute Stroke (In Vivo Data)6.1 HDLs and Acute Stroke: Experimental ModelsTherapeutic Potential of HDL in Cardioprotection and Tissue Repair1 Introduction2 In Vitro Effects of HDL on Cardiomyocytes2.1 Effects of HDL in Rat Neonatal Cardiomyocytes2.2 Adult Mouse Cardiomyocytes2.3 Apo A-I and Sphingosine-1-Phosphate Mediate the Cytoprotective Effects of HDL3 HDL Confer Protection Against Ischaemia Reperfusion Injury3.1 IRI in the Isolated Heart Model3.2 IRI in In Vivo Models3.3 Apo A-I and S1P Confer Cardioprotective Effects on HDL4 Human Apo A-I Gene Transfer Attenuates Diabetic Cardiomyopathy4.1 Human Apo A-I Gene Transfer Influences Metabolic Parameters in Streptozotocin-Induced Diabetes Mellitus4.2 Human Apo A-I Gene Transfer Attenuates DiabetesAssociated Oxidative Stress, Cardiac Fibrosis,4.3 Human Apo A-I Gene Transfer Reduces Diabetes-Induced Cardiac Inflammation4.4 Human Apo A-I Gene Transfer Reduces Diabetes-Associated Cardiac Apoptosis and Improves the Cardiac Endothelial Integrity5 HDL and Tissue Repair: Modulation of EPC Biology via SR-BI6 Development of Topical HDL Therapy for Cutaneous Wound Healing7 Beneficial Effects of Selective HDL-Raising Gene Transfer on Cardiac Remodelling and Cardiac Function After Myocardial Infarction in MicePart IV Treatments for Dyslipidemias and Dysfunction of HDLHDL and Lifestyle Interventions1 HDL and Diet1.1 Effects of Substituting Dietary Saturated Fatty Acids1.2 Dietary MUFA1.3 n-3 Polyunsaturated Fatty Acids1.4 Carbohydrate and Extrinsic Sugars1.5 Effects of Dietary Fatty Acids and Cholesterol on HDL Function2 Weight Loss2.1 Impact of Adiposity on HDL Concentration and Function2.2 Effect of Weight-Loss Therapies on HDL Concentration and Function3 Effects of Regular Aerobic Exercise3.1 Effects of Exercise on HDL3.2 Effects of Exercise on Prevention and Treatment of Cardiometabolic Risk4 Smoking Cessation4.1 Smoking and HDL-C Concentration4.2 Potential Mechanisms for the Smoking-Related Reduction in HDL-C4.3 Smoking Cessation Intervention to Increase Plasma HDL Concentration5 Effects of Alcohol on HDL and Cardiovascular Risk5.1 Alcohol Intake and HDL-C5.2 Effects of Alcohol on HDL Atheroprotective FunctionsEffects of Established Hypolipidemic Drugs on HDL Concentration, Subclass Distribution, and Function1 Effects on Plasma HDL-C Concentration1.1 Statins1.2 Fibrates1.3 Niacin2 Effects on HDL Subclass Distribution2.1 Statins2.2 Fibrates2.3 Niacin3 Effects on Cholesterol Efflux Capacity3.1 Statins3.2 Fibrates3.3 Niacin4 Effect on HDL Ability to Preserve Endothelial Cell Homeostasis4.1 Statins4.2 Fibrates4.3 Niacin5 Effect on HDL Antioxidant Properties5.1 Statins5.2 Fibrates5.3 NiacinEmerging Small Molecule Drugs1 Introduction2 Cholesteryl Ester Transfer Protein Inhibitors2.1 Biological Mechanisms2.2 Current State2.3 Future Perspectives3 Novel PPAR Agonists3.1 Biological Mechanisms3.2 Current State3.3 Future Perspectives4 Novel LXR Agonists4.1 Biological Mechanisms4.2 Current State4.3 Future Perspectives5 RVX-2085.1 Biological Mechanisms5.2 Current StateApoA-I Mimetics1 Introduction2 ApoA-I Mimetic Peptides2.1 4F2.2 6F2.3 FX-5A2.4 ATI-52612.5 ETC-6423 ApoA-I-Based Infusion Therapy3.1 HDL-VHDL Infusions3.2 Purified ApoA-I Infusions3.4 CSL-111 and CSL-112 Infusions3.5 CER-001 Infusions3.6 Modified ApoA-I4 Selective DelipidationAntisense Oligonucleotides, microRNAs, and Antibodies1 Antisense Oligonucleotides1.1 Making Sense of Antisense1.2 Therapeutic Antisense Oligonucleotides to Treat Dyslipidemia1.3 Therapeutic Antisense Oligonucleotides for the Increase of HDL-Cholesterol Levels and Improvement of HDL Function2 miRNAs2.1 miRNA-Based Therapy2.2 Micromanaging Cholesterol Efflux, RCT, HDL Levels, and HDL Function3 Antibodies3.1 LDL-Cholesterol Lowering Approaches: Proprotein Convertase Subtilisin/Kexin Type 9 Blocking Antibodies3.2 Approaches to Antibody Therapy for the Increase of HDLCholesterol Levels3.3 Effect of Antibodies Used for the Treatment of Chronic Inflammatory Diseases on HDL Antiatherogenic Functions3.4 Vaccines Against Atherosclerosis
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