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High Density Lipoproteins : From Biological Understanding to Clinical Exploitation.

Bibliographic Details
Main Author: von Eckardstein, Arnold.
Other Authors: Kardassis, Dimitris.
Format: eBook
Language:English
Published: Cham : Springer International Publishing AG, 2015.
Edition:1st ed.
Series:Handbook of Experimental Pharmacology Series
Subjects:
Electronic books.
Online Access:Click to View
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.

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