Human Apolipoprotein Mutants III: Diagnosis and Treatment

ISBN-13: 9783642846366 / Angielski / Miękka / 2011 / 291 str.

Cesare R. Sirtori; Guido Franceschini; Bryan H. Jr. Brewer

Opis

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.

Spis treści

Enzymes and Apolipoproteins in the Diagnosis of Disease.- Lipoprotein Lipase: Gene Variants and Coronary Atherosclerosis.- Apolipoproteins in the Diagnosis of Disease: Cerebral and Peripheral Atherosclerosis.- Structural and Functional Relationships in Apolipoproteins.- Functional Properties of Discoidal Apoprotein/Phospholipid Complexes: Cholesterol Efflux from Macrophages and Conversion by Lecithin-Cholesterol Acyl Tansferase.- Lipid Transport by Apolipoprotein AI: Structure and Function.- Characterization of Lipoprotein Particles Containing Apolipoprotein A-IV.- Structural and Functional Properties of Apo A-I Variants in Reconstituted HDL.- Structural Domains in Human Serum Low Density Lipoprotein Apolipoprotein B100.- Crystal Structures of the Common Apolipoprotein E Variants: Insights into Functional Mechanisms.- Analysis of Apolipoprotein E Function in Adrenal Cells: Effects on Cholesterol Metabolism and Signal Transduction Pathways.- Animal Models in the Apolipoprotein Mutant Research.- Spontaneous Hypercholesterolemia in Pigs.- The Apolipoprotein E Cys-142 Mutant: Role in Dominant Inheritance of Type III Hyperlipoproteinemia and Expression in Transgenic Mice.- Recombinant Apolipoproteins as Drugs.- Apolipoproteins as “Drugs”: Current Status.- Non-Mammalian Host System for the Expression of Mammalian Apolipoproteins.- Recombinant Human Proapolipoprotein A-I: Experimental Strategies for the Production of an Authentic Molecule.- The Role of HDL Apolipoproteins in Mediating HDL Receptor Binding and Intracellular Cholesterol Efflux.- Molecular Abnormalities of Apolipoproteins.- The Metabolism of Truncated Forms of Apolipoprotein B in Hypobetalipoproteinemia.- Apolipoprotein B: Genetic Variants Provide Insight Into Structure and Function.- The Mutations of Apolipoprotein B Gene Causing Hypobetalipoproteinemia: Molecular and Functional Abnormalities in Apo B-87Padova.- Causes Underlying the Reduced Response to Simvastatin Treatment in Hypercholesterolemic Patients.- Molecular Genetics of the Familial Chylomicronemia Syndrome.- Rare Mutations in the Apo E Gene Associated with Dominant Mode of Inheritance of Familial Dysbetalipoproteinemia (FD).- Identification of Common Genetic Polymorphisms that Determine Plasma Levels of Apo Al and HDL-C.- Structure-Function Relationships of Apolipoprotein A-I Variants.- Sex-Related Differences in the Phenotypic Expression of the Apolipoprotein A-Imllano mutant.- Human Apolipoprotein A-IV.