Low Density Lipoproteins

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.