High Density Lipoproteins : : From Biological Understanding to Clinical Exploitation.

• Superior document: Handbook of Experimental Pharmacology Series ; v.224
• Author: von Eckardstein, Arnold.
• TeilnehmendeR: Kardassis, Dimitris.
• Place / Publishing House: Cham : : Springer International Publishing AG,, 2015.; ©2015.
• Year of Publication: 2015
• Edition: 1st ed.
• Language: English
• Series: Handbook of Experimental Pharmacology Series
• Physical Description: 1 online resource (694 pages)

Table of Contents

Intro -- Preface -- Acknowledgement -- Contents -- Part I: Physiology of HDL -- Structure of HDL: Particle Subclasses and Molecular Components -- 1 HDL Subclasses -- 2 Molecular Components of HDL -- 2.1 Proteome -- 2.1.1 Major Protein Components -- Apolipoproteins -- Enzymes -- Lipid Transfer Proteins -- Acute-Phase Response Proteins -- Complement Components -- Proteinase Inhibitors -- Other Protein Components -- Heterogeneity in HDL Proteins -- 2.1.2 Protein Isoforms, Translational and Posttranslational Modifications -- 2.2 Lipidome -- 2.2.1 Phospholipids -- 2.2.2 Sphingolipids -- 2.2.3 Neutral Lipids -- 3 The Structure of HDL -- 3.1 Introduction/Brief History -- 3.2 HDL in the Test Tube -- 3.2.1 Discoid HDL -- 3.2.2 Spherical rHDL -- 3.3 ``Real ́́HDL Particles -- Conclusions and Perspectives -- References -- HDL Biogenesis, Remodeling, and Catabolism -- 1 Biogenesis of HDL -- 1.1 ATP-Binding Cassette Transporter A1 (ABCA1) -- 1.1.1 Structure of apoA-I and Its Interactions with ABCA1 In Vitro -- 1.1.2 Interaction of apoA-I with ABCA1 In Vivo Initiates the Biogenesis of HDL -- 1.1.3 Unique Mutations in apoA-I May Affect apoA-I/ABCA1 Interactions and Inhibit the First Step in the Pathway of HDL Biogene... -- 1.2 Lecithin/Cholesterol Acyltransferase (LCAT) -- 1.2.1 Interactions of Lipid-Bound ApoA-I with LCAT -- 1.2.2 ApoA-I Mutations that Affect apoA-I/LCAT Interactions -- 1.3 ApoA-I Mutations May Induce Hypertriglyceridemia and/or Hypercholesterolemia -- 1.3.1 Potential Mechanism of Dyslipidemia Resulting from apoA-I Mutations -- 1.4 ApoE and apoA-IV Participate in the Biogenesis of HDL Particles Containing the Corresponding Proteins -- 1.5 Clinical Relevance of the Aberrant HDL Phenotypes -- 2 Remodeling and Catabolism of HDL -- 2.1 ATP-Binding Cassette Transporter G1 -- 2.2 Phospholipid Transfer Protein -- 2.3 apoM.

2.4 Hepatic Lipase and Endothelial Lipase -- 2.5 Cholesteryl Ester Transfer Protein -- 2.6 Scavenger Receptor BI -- 2.6.1 Role of SR-BI in HDL Remodeling Based on Its In Vitro Interactions with Its Ligands -- 2.6.2 In Vivo Functions of SR-BI -- 2.7 Role of Ecto-F1-ATPase/P2Y13 Pathway in Hepatic HDL Clearance -- 2.8 Transcytosis of apoA-I and HDL by Endothelial Cells -- 2.9 The Role of Cubilin in apoA-I and HDL Catabolism by the Kidney -- 3 HDL Subclasses -- 3.1 The Origin and Metabolism of Prebeta-HDL Subpopulations -- 3.2 Complexity of HDL -- 4 Sources of Funding -- References -- Regulation of HDL Genes: Transcriptional, Posttranscriptional, and Posttranslational -- 1 Regulation of Genes Involved in HDL Metabolism at the Transcriptional Level -- 1.1 General Introduction to Hormone Nuclear Receptors -- 1.2 Transcriptional Regulation of the apoA-I Gene in the Liver -- 1.2.1 The Role of the Distal Enhancer in apoA-I Gene Transcription -- 1.2.2 Other Factors Regulating apoA-I Gene Transcription -- 1.3 Transcriptional Regulation of the ABCA1 Gene -- 1.3.1 Upregulatory Mechanisms of ABCA1 Gene Expression -- 1.3.2 Negative Regulation of ABCA1 Gene Transcription -- 1.4 Transcriptional Regulation of the ABCG1 Gene -- 1.5 Transcriptional Regulation of the Apolipoprotein E Gene -- 1.5.1 Proximal Regulatory Binding Sites Involved in the apoE Gene Expression -- 1.5.2 Distal Regulatory Binding Sites That Modulate apoE Gene Expression in Macrophages -- 1.6 Transcriptional Regulation of the Human apoM Gene in the Liver -- 1.7 Transcriptional Regulation of the CETP Gene -- 1.8 Transcriptional Regulation of the PLTP Gene -- 1.9 Transcriptional Regulation of the Bile Acid Transporters ABCG5/ABCG8 -- 1.10 Transcriptional Regulation of the HDL Receptor SR-BI -- 2 Posttranscriptional Regulation of HDL Genes by Noncoding RNAs and microRNAs.

2.1 miRNAs: Biogenesis and Function -- 2.2 Posttranscriptional Modulation of HDL Metabolism by miRNAs -- 2.2.1 Targeting ABCA1 and ABCG1 -- 2.2.2 Targeting SR-BI -- 2.2.3 Targeting Other miRNAs Related to HDL Biogenesis and Function -- 3 Posttranslational Mechanisms of HDL Regulation -- 3.1 ABCA1 -- 3.2 ABCG1 -- 3.3 SR-BI -- Conclusions -- References -- Cholesterol Efflux and Reverse Cholesterol Transport -- 1 Cholesterol Efflux as the First Step of Reverse Cholesterol Transport (RCT) -- 1.1 ABCA1-Mediated Lipid Efflux to Lipid-Poor apoA-I -- 1.2 Cholesterol Efflux to Lipidated HDL -- 2 HDL Quality and Cholesterol Efflux -- 3 RCT in Animal Models -- 3.1 Physiology -- 3.1.1 Methodological Approaches to Quantify RCT In Vivo -- 3.1.2 Factors Impacting In Vivo RCT -- 3.2 Pharmacology -- 3.2.1 CETP Inhibitors -- 3.2.2 Nuclear Receptor Activation -- 3.2.3 Cholesterol Absorption Inhibitors -- 3.2.4 Augmenting or Mimicking apoA-I -- 4 Serum Cholesterol Efflux Capacity (CEC) -- Conclusions -- References -- Functionality of HDL: Antioxidation and Detoxifying Effects -- 1 High-Density Lipoproteins and Oxidative Stress -- 1.1 High-Density Lipoproteins: Antioxidative Function -- 1.2 Mechanisms of Protection -- 1.3 Heterogeneity of Antioxidant Activity of HDL Particles -- 2 High-Density Lipoproteins, Paraoxonase-1 -- 2.1 PON1 as an Antioxidant -- 2.2 PON1 and Bacterial Pathogens -- 3 High-Density Lipoproteins, Environmental Pathogens and Toxins -- 3.1 Bacterial Pathogens -- 3.2 Parasites -- 3.3 Hepatitis, Dengue and Other Viruses -- 3.4 Metal Oxides, Carbon Nanotubes and PLGA Nanoparticles -- 3.5 PON1 and Organophosphates -- 3.6 Detoxification of Plasma and External Fluids -- References -- Signal Transduction by HDL: Agonists, Receptors, and Signaling Cascades -- 1 Introduction -- 2 ApoA-I-Induced Cell Signaling Directly Mediated by ABCA1.

3 ApoA-I-Induced Cell Signaling Indirectly Mediated by beta-ATPase and P2Y12/13 ADP Receptor -- 4 ApoA-I- and HDL-Induced Cell Signaling Indirectly Mediated by ABCA1 and/or ABCG1 -- 5 HDL-Induced Cell Signaling Mediated by SR-BI -- 6 HDL-Induced Cell Signaling Mediated by S1P -- 7 HDL-Induced Cell Signaling: Future Challenges and Opportunities -- References -- Part II: Pathology of HDL -- Epidemiology: Disease Associations and Modulators of HDL-Related Biomarkers -- 1 Protective Role of HDL: Evidence from Epidemiological Studies -- 2 HDL Cholesterol as a Risk Factor for Atherosclerosis and Its Complications -- 3 HDL Cholesterol as a Risk Factor for Other Diseases -- 4 Total HDL-C in Various Populations -- 5 Total HDL-C Modulated by Environmental Factors -- 6 HDL-C in Diseases and Conditions -- 7 High HDL Levels Do Not Add to the Protection -- 8 Effect of HDL on Stroke -- 9 Time Trends in Total HDL-C -- 10 Are There Other Biomarkers than the Total HDL-C? -- 11 HDL Fractions -- 12 HDL Particle Size -- 13 HDL Particle Number -- 14 HDL Lipids -- 15 HDL Apolipoproteins -- 16 HDL Proteomics -- 17 HDL Function -- 18 Pleiotropy -- 19 Future Approaches of Epidemiological Studies -- Conclusion -- References -- Beyond the Genetics of HDL: Why Is HDL Cholesterol Inversely Related to Cardiovascular Disease? -- 1 General -- 2 Determinants of Plasma HDL Cholesterol Levels -- 2.1 Established Primary Regulators of Plasma HDL Cholesterol -- 2.2 Established Secondary Regulators of Plasma HDL Cholesterol -- 2.3 Missing Heritability -- 3 Novel Insight into HDL Biology -- 3.1 De Novo Synthesis of HDL and HDL Binding -- 3.1.1 Bone Morphogenetic Protein-1 and Procollagen C-Proteinase Enhancer-2 -- 3.1.2 Apolipoprotein M -- 3.1.3 CTP:Phosphocholine Cytidylyltransferase Alpha (CT Alpha) -- 3.1.4 Apolipoprotein F -- 3.1.5 Glucuronic Acid Epimerase.

3.1.6 Beta-Chain of ATP Synthase -- 3.2 HDL Conversion and Remodeling -- 3.2.1 Angptl Family of Proteins -- 3.2.2 Tribbles Homolog 1 -- 3.2.3 Tetratricopeptide Repeat Domain/Glycogen-Targeting PP1 Subunit G(L) -- 3.2.4 ppGalNAc-T2 -- 3.2.5 Glucokinase (Hexokinase 4) Regulator -- Conclusions and Perspectives -- References -- Mouse Models of Disturbed HDL Metabolism -- 1 Introduction -- 2 Apolipoprotein A-I -- 3 ATP-Binding Cassette Transporter A1 -- 4 ATP-Binding Cassette Transporter G1 -- 5 Lecithin-Cholesterol Acyltransferase -- 6 Phospholipid Transfer Protein -- 7 Scavenger Receptor BI -- 8 Insights from Intercrossing of the Different Knockout Mice -- 9 Conclusions from the Gene Knockout Mouse Studies -- 10 Cholesterol Ester Transfer Protein Transgenic Mice -- Concluding Remark -- References -- Dysfunctional HDL: From Structure-Function-Relationships to Biomarkers -- 1 Introduction -- 2 HDL and Reverse Cholesterol Transport -- 2.1 Mechanisms Under Physiological Conditions -- 2.2 Alterations of the Cholesterol Efflux Capacity of HDL in Cardiovascular Disease -- 3 Effects of HDL on LDL Oxidation -- 3.1 Mechanisms Under Physiological Conditions -- 3.2 Impairment of the Anti-Oxidative Effects of HDL in Patients After Surgery and With Cardiovascular Disease -- 4 Effects of HDL on Endothelial Nitric Oxide Bioavailability -- 4.1 Mechanisms Under Physiological Conditions -- 4.2 Impaired HDL Capacity to Stimulate NO Production in Patients with Cardiovascular Disease -- 5 Endothelial Anti-Inflammatory Effects of HDL -- 5.1 Mechanisms Under Physiological Conditions -- 5.2 Impaired Endothelial Anti-Inflammatory Effects of HDL in Patients with CAD, Diabetes, or Chronic Kidney Dysfunction -- 6 Effects of HDL on Endothelial Cell Apoptotic Pathways -- 6.1 Mechanisms Under Physiological Conditions.

6.2 Impairment of the Endothelial Anti-Apoptotic Effects of HDL in Patients with Cardiovascular Disease.