The proposed program which consists of seven Projects and two Core resources involves the sustained efforts of several members of the University of Chicago in an attempt to examine surface phenomena involved in protein-lipid interactions, lipoprotein-lipoproteins interactions, lipoproteins and lipid-modifying enzymes (phospholipase, LCAT, hepatic lipase), lipoproteins and cells (blood granulocy tes, lymphocytes and monocytes, skin fibroblasts an rat neuroblastoma). The work will focus on high density (HDL); low-density lipoproteins (LDL) and model systems and will attempt to establish the relationship between the structure of their main apoproteins (A-I, A-II and B) and lipoprotein class heterogeneity. The in vitro studies will involve a series of physical, chemical and immunological techniques to be applied to the analysis of the lipoprotein sub-classes of three animal species, man, dog and African green monkeys, animals which exhibit important differences in their lipoprotein and apoprotein makeup. The interaction between lipoprotein and cells will be studied both on a structural and functional level and will attempt to define the mode of binding HDL to the cell membrane, on the role played by lipoproteins in the regulation of cholesterol and glycosphingolipid synthesis and as mediators of the cellular effect by oxygenated sterols. The in vivo studies are expected to complement the in vitro observations on the issues of lipoprotein interactions and subclass heterogeneity. In the latter case, studies of families of African green monkeys are expected to provide an insight into the genetic determination of this heterogeneity and its significance in terms of the response of the animals to diets leading to hyperlipidemia. Overall, the integrated efforts of this Program Project should provide an insight into the roles played by the lipoprotein surface in lipoprotein metabolism both in normo, and hyperlipidemia.
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