Human Apolipoprotein Mutants III: Diagnosis and Treatment (Nato ASI Subseries H:, 73)

Hopes to develop apolipoproteins for diagnostic or, even better, therapeuticpurposes are growing. Areas of use may range from arterial disease to AIDS, fertilization programs, neurological or inflammatory disorders, and the like. However, these young members of the large family of circulating proteins still deserve careful study, both in terms of structural and functional properties and of their pathological changes. In addition, related molecules, in particular belonging to the family of enzymes, such as lipases and acyltransferases, offer exciting insight into the mechanisms of regulation of lipid transport and exchange. Described hereis the use of apolipoproteins and enzymes in the diagnosis of coronary and cerebrovascular disease. Structural and functional changes of apolipoproteins are related to lipid transport and binding to different receptors. Further, the development of apolipoprotein drugs and their possible clinical use for vascular and non vascular disease is discussed and finally an overview on lipoprotein transformation processes, expression systems and natural mutants is provided. Front Matter....Pages I-XI Lipoprotein lipase: Gene variants and coronary atherosclerosis....Pages 1-11 Apolipoproteins in the Diagnosis of Disease: Cerebral and Peripheral Atherosclerosis....Pages 13-20 Functional Properties of Discoidal Apoprotein/Phospholipid Complexes: Cholesterol Efflux from Macrophages and Conversion by Lecithin-Cholesterol Acyl Transferase....Pages 21-30 Lipid Transport by Apolipoprotein AI: Structure and Function....Pages 31-41 Characterization of Lipoprotein Particles Containing Apolipoprotein A-IV....Pages 43-52 Structural and Functional Properties of Apo A-I Variants in Reconstituted HDL....Pages 53-65 Structural Domains in Human Serum Low Density Lipoprotein Apolipoprotein B100....Pages 67-79 Crystal Structures of the Common Apolipoprotein E Variants: Insights into Functional Mechanisms....Pages 81-96 Analysis of Apolipoprotein E Function in Adrenal Cells: Effects on Cholesterol Metabolism and Signal Transduction Pathways....Pages 97-106 Spontaneous Hypercholesterolemia in Pigs....Pages 107-112 The Apolipoprotein E Cys-142 Mutant: Role in Dominant Inheritance of Type III Hyperlipoproteinemia and Expression in Transgenic Mice....Pages 113-120 Apolipoproteins as “Drugs”: Current Status....Pages 121-133 Non-Mammalian Host Systems for the Expression of Mammalian Apolipoproteins....Pages 135-143 Recombinant Human Proapolipoprotein A-I: Experimental Strategies for the Production of an Authentic Molecule....Pages 145-163 The Role of HDL Apolipoproteins in Mediating HDL Receptor Binding and Intracellular Cholesterol Efflux....Pages 165-173 The Metabolism of Truncated Forms of Apolipoprotein B in Hypobetalipoproteinemia....Pages 175-182 Apolipoprotein B: Genetic Variants Provide Insight into Structure and Function....Pages 183-194 The Mutations of Apolipoprotein B Gene Causing Hypobetalipoproteinemia: Molecular and Functional Abnormalities in Apo B-87 Padova ....Pages 195-206 Causes Underlying the Reduced Response to Simvastatin Treatment in Hypercholesterolemic Patients....Pages 207-229 Molecular Genetics of the Familial Chylomicronemia Syndrome....Pages 231-239 Rare mutations in the APOE gene associated with dominant mode of inheritance of Familial Dysbetalipoproteinemia (FD)....Pages 241-246 Identification of Common Genetic Polymorphisms that Determine Plasma Levels of ApoAI and HDL-C....Pages 247-256 Structure-Function Relationships of Apolipoprotein A-I Variants....Pages 257-265 Sex-Related Differences in the Phenotypic Expression of the Apolipoprotein A-I Milano Mutant....Pages 267-277 Human Apolipoprotein A-IV....Pages 279-287 Back Matter....Pages 289-294