Low Density Lipoproteins

ISBN-13: 9781468422528 / Angielski / Miękka / 2012 / 446 str.

Charles Day

Opis

Low density lipoproteins (LDL) are pathophysiologically important be cause of their central role in the disease atherosclerosis and because atherosclerosis is the leading cause of death in developed countries. Many researchers believe that a more detailed knowledge of the struc ture, function, and metabolism of LDL may eventually lead to a means to control atherosclerosis. For this reason a fairly large research effort has gone into the investigation of LDL over the past few years. The purpose of this book is to collect and summarize in one place most of the pub lished information on LDL through 1975. To this end more than 1500 references are cited in the papers that make up this volume. The A, B, C apolipoprotein classification system was adopted for use throughout this work. In addition to the A, B, C, and "D" families of apolipoproteins, apoE is used to designate the "arginine-rich" apolipo protein. This classification system is used because it is far less cumber some than other proposed classification schemes for apolipoproteins."

Spis treści

I. Isolation and Structure.- 1 Isolation and Characterization of Low Density Lipoproteins.- I. Introduction.- A. The Origin and Definition of the Term “Low Density Lipoproteins”.- B. Nomenclature Based on Protein Moieties.- II. Isolation Methods.- A. Electrophoretic Technique.- B. Chemical Fractionation.- C. Immunochemical Fractionation.- D. Chromatographic Techniques.- E. Ultracentrifugation.- III. Preservation of LDL.- IV. Assessment of Purity.- A. Analytical Ultracentrifugation.- B. Zonal Electrophoresis.- C. Immunology.- V. Immunochemical and Chemical Properties of LDL and LP-B.- A. Immunochemical Properties.- B. Lipid and Protein Composition.- C. Amino Acid Composition.- D. Studies of the Protein Moieties.- E. Composition and Concentration of Apolipoproteins in LDL Subfractions.- VI. Physicochemical Properties of LDL and LP-B with an Interpretation of Molecular Species.- VII. Conclusions.- References.- 2 Physicochemical Characterization of Low Density Lipoproteins.- I. Introduction.- II. Hydrodynamic Analysis. Compositional and Structural Heterogeneity.- III. Morphology.- A. Electron Microscopy.- B. Small-Angle X-Ray Scattering.- IV. Internal Structure and Molecular Interactions.- A. The Organization and Physical State of Lipids.- B. The Disposition and Conformation of Protein.- V. Summary and Conclusions.- References.- II. Metabolism.- 3 Mechanisms of Formation of Low Density Lipoproteins: Metabolic Pathways and their Regulation.- I. Introduction.- II. Composition and Structure.- III. Metabolic Conversion of Lipoproteins.- A. Human.- B. Rat.- IV. Mechanism of Formation of Intermediate Lipoproteins.- V. LDL Synthesis: An Integrated Scheme and Possible Regulatory Mechanisms.- A. General Considerations.- B. Synthesis of Triglyceride-Rich Lipoproteins.- C. Formation of Intermediate Lipoproteins.- D. Clearance of Intermediate Lipoproteins without Conversion to LDL.- E. Conversion of Intermediate Lipoproteins to LDL.- F. Removal of LDL from Circulation.- VI. Conclusions.- References.- 4 Interactions of Lipoproteins with Cells in Culture.- I. Introduction.- II. Interactions of Lipoproteins with Human Fibroblasts: The LDL Receptor.- III. Interactions of Lipoproteins with Other Cell Types.- IV. Interactions of Lipoproteins with Smooth Muscle Cells: Cell Proliferation.- References.- 5 Lipoprotein Lipid Exchange in Biological Systems.- I. Introduction.- II. Phospholipid Exchange.- A. Exchange between Lipoproteins.- B. Exchange between Lipoproteins and Cells, Membranes, and Tissues.- III. Cholesterol Exchange.- A. Exchange between Lipoproteins.- B. Exchange between Lipoproteins and Cells, Membranes, and Tissues.- IV. Cholesteryl Ester Exchange.- V. Triglyceride Exchange.- VI. Unesterified Fatty Acid Exchange.- VII. ?-Tocopherol Exchange.- VIII. Factors Modifying Lipid Exchange.- A. Temperature.- B. Organic Solvents.- C. Surface Charge.- D. Exchange Proteins.- E. Lipoprotein Fatty Acid Composition.- F. Lecithin:Cholesterol Acyltransferase (LCAT).- IX. Physiological Significance of Lipid Exchange.- X. Possible Mechanisms of Lipid Exchange.- References.- 6 Effect of Exercise on Serum Lipids and Lipoproteins.- I. Exercise and Serum Cholesterol.- II. Exercise and Serum Triglycerides.- III. Exercise and Serum Phospholipids.- IV. Exercise and Serum Lipoproteins.- V. Exercise and Metabolism of Serum Lipids and Lipoproteins.- VI. Conclusions.- References.- III. Aberrations of Metabolism.- 7 The Hyper-?- and Hyperpre-?-lipoproteinemias.- I. Introduction.- II. The Hyperlipoproteinemic Syndromes.- A. Hyper-?-lipoproteinemia.- B. Combined Hyperlipoproteinemia.- C. Hyperpre-?-lipoproteinemia.- D. Sporadic Hyperlipoproteinemia.- III. The Structure of LDL in Hyperlipoproteinemia.- IV. Metabolic Derangements in the Synthesis of LDL.- A. The Enzymatic Hydrolysis of VLDL Triglyceride.- B. Kinetic Studies on VLDL Triglyceride Metabolism in Hyperlipoproteinemia.- C. Kinetic Studies on Apolipoprotein Metabolism in Hyperlipoproteinemia.- V. Metabolic Derangements in the Catabolism of LDL.- VI. Variables in the Physiologic Control of Lipoprotein Metabolism.- A. The Control of VLDL Synthesis.- B. The Conversion of VLDL to LDL.- VII. Pharmacologic Control of Lipoprotein Metabolism.- A. Nicotinic Acid.- B. Clofibrate.- C. Cholestyramine.- VIII. Conclusions.- References.- 8 Type III Hyperlipoproteinemia.- I. Definition and History.- II. Plasma Lipids and Lipoproteins.- A. Classes of Lipoproteins.- B. Lipoproteins of Density 1.006–1.019 (LP-III, Intermediate Density Lipoprotein, or IDL).- C. VLDL (d 0.95–1.006, Sf 20–400).- D. LDL (d 1.019–1.063, Sf 0–12).- E. Chylomicrons (d 400).- F. HDL (d 1.063–1.210, F1.21 0–9).- III. Metabolic Defect.- IV. Diagnosis.- V. Clinical Features.- A. Age of Detection.- B. Vascular Disease.- C. Xanthomatosis.- D. Other Clinical Features.- VI. Treatment.- VII. Genetics.- VIII. Summary.- References.- 9 Lp(a) Lipoproteins and the Genetic Polymorphisms of Lipoprotein B.- I. Introduction: Nomenclature and Abbreviations.- II. Historical Development.- III. Inherited Variants of Human Serum ?-Lipoproteins.- A. The Ag System.- B. Relationship of the Ag System to Lp(a) Lipoproteins.- C. Nature of the Ag Antigen.- D. Other Polymorphic Systems of Human Serum ?-Lipoproteins.- IV. Lp(a) Lipoproteins.- A. Genetics of Lp(a) Lipoproteins.- B. Possibility of Heterogeneity of the Lp(a) Factor: The Lp(x) Antigen.- C. Methods for Demonstration of Lp(a) Lipoproteins.- D. Isolation and Purification of Lp(a) Lipoproteins.- E. Chemical and Physicochemical Properties of Lp(a) Lipoproteins.- F. Distribution of Lp(a) Polypeptides among Lipoproteins of Different Density Classes.- G. Lp(a) Lipoprotein Values in the Normal Population.- H. Lp(a) Lipoproteins in Species Other than Man.- I. Relationship of Lp(a) to Histocompatibility Antigens.- J. Lp(a) Lipoproteins, Hyperlipoproteinemia, and Atherosclerosis.- K. Lp(a) Lipoproteins and Liver Diseases.- V. Summary and Conclusions.- References.- 10 Abetalipoproteinemia.- I. Introduction.- II. The Lipoproteins and Apoproteins.- A. HDL and Its Apoproteins.- B. Lipoproteins with Density Less than 1.063 g/ml.- III. LCAT Activity.- IV. Genetic Aspects.- V. Conclusions.- References.- IV. Comparative Biology.- 11 Mammalian Low Density Lipoproteins.- I. Introduction.- II. General Studies.- III. Rats.- A. Normolipidemia: Properties of LDL.- B. LDL Metabolism.- C. Hypolipidemia: Orotic Acid and Essential Fatty Acid Deficiency.- D. Hyperlipidemia.- E. Hypolipidemia: CPIB, Tomatine, Glucagon.- IV. Guinea Pigs.- A. Normolipidemia: Properties of LDL.- B. Hyperlipidemia.- C. LDL Metabolism.- V. Rabbits.- A. Normolipidemia: Properties of LDL.- B. Hyperlipidemia.- C. Physiological Changes.- VI. Ungulates.- A. Cattle.- B. Sheep.- C. Swine.- D. Horses.- VII. Marine Mammals.- A. Killer Whales.- B. Dolphins.- C. Sea Lion, Walrus, and Harbor Seal.- VIII. Dogs.- A. Normolipidemia.- B. Hyperlipidemia.- C. LDL Metabolism.- D. Bile Duct Obstruction.- IX. Cats.- X. Nonhuman Primates.- A. General Considerations.- B. Family Cercopithecoidea (Old World Monkeys).- C. Family Pongidae, Genus Pan (Chimpanzee).- D. Family Cebidae (New World Monkeys).- XI. Conclusion.- References.- 12 Low Density Lipoproteins of Nonmammalian Vertebrates.- I. Introduction.- II. Occurrence and Characteristics of “Normal” LDL of Fish, Amphibia, Reptiles, and Birds.- A. General Comments.- B. Flotation Studies of Lipoproteins and Lipid Analyses.- C. Electrophoretic Studies.- D. Apoprotein Analyses.- III. Effects of Estrogens and Other Hormones on Rates of Synthesis and Composition of LDL.- IV. Correlation between LDL of Plasma and Liver Structure.- V. Functional Roles of LDL and VLDL in Nonmammalian Vertebrates.- VI. Manipulation of Light Lipoproteins in Nonmammalian Vertebrates.- A. Cholesterol Feeding.- B. Feeding of Specific Fatty Acids and Unique Lipids.- C. Fasting or Overfeeding.- D. Ionizing Radiation and Pesticides.- E. Temperature.- VII. Summary.- References.- V. Relationship to Atherosclerosis.- 13 Interaction of Low Density Lipoproteins with Arterial Constituents: Its Relationship with Atherogenesis.- I. General Considerations.- II. Irritative Components of LDL.- III. Passage of LDL across the Endothelial Barrier.- IV. Arterial Wall Components that Interact with LDL.- A. Enzymes Acting upon LDL.- B. Elastin.- C. Complex Macromolecules.- V. Affinity of LCF for Serum LDL from Coronary Heart Disease Patients.- References.- 14 Interaction of Low Density Lipoproteins with Small and Large Molecules.- I. Introduction.- II. Interaction with Small Ions and Molecules.- A. Binding of Hydrogen Ions.- B. Binding of Metal Ions.- C. Binding of Free Fatty Acids (FFA).- D. Interaction with ANS.- III. Interaction of LDL with Macromolecules in Solution.- A. Components of the Extracellular Matrix of the Arterial Wall.- B. Mucopolysaccharide-LDL Interaction.- C. Heparin-LDL Interaction.- D. Dextran Sulfate-LDL Interaction.- E. Amylopectin Sulfate-LDL Interaction.- F. Collagen-LDL Interaction.- G. Elastin-LDL Interaction.- H. Interaction with Nonionic Polymers.- IV. Interaction at the Tissue Level.- A. Isolation of Complexes from Arterial Tissue.- B. Interaction of LDL in a Gel Matrix.- V. Nature of the Interaction between LDL and Polyanions.- A. Ionic Aspects of the Interaction.- B. Specific Features of the Polysaccharides Affecting Complex Formation.- C. Nonionic Aspects of the Interaction.- References.- 15 Control of Low Density Lipoproteins and Atherosclerosis with the Bile Acid Sequestrants Colestipol, Cholestyramine, and Polidexide.- I. Introduction.- II. Colestipol.- A. Effect on Serum Cholestrol and Triglycerides.- B. Effect on Serum Lipoproteins.- C. Modification of Cholesterol Metabolism.- D. Reduction of Cardiovascular Mortality.- E. Side Effects.- III. Cholestyramine.- A. Effect on Serum Lipids, Lipoproteins, and Cholesterol Metabolism.- B. Effect on Atherosclerosis.- C. Side Effects.- IV. Polidexide.- V. Conclusions.- References.