The high density lipoproteins (HDL) are a collection of discrete complexes (HDL subspecies), a significant portion of which are derived directly or indirectly from the small intestine. HDL perform a number of important and diverse functions, each of which can possibly be attributed to a single HDL subspecies. However, the functions of individual subspecies and their relationship to the intestine are not well defined because the HDL subspecies are not been completely separated and identified. One goal of this project will be to isolate and characterize each individual HDL subspecies. All the apo A-I-containing lipoproteins will be isolated from plasma in a minimally perturbing manner using a new method, selected affinity immunosorption. Each HDL subspecies will then be isolated by a logical succession of proven isolation methods, including secondary immunosorption, starch block electrophoresis, preparative isoelectric focusing, HPLC, preparative electrophoresis, and selective chromatographic methods. In parallel, a method will be developed to determine quantitatively the levels of each HDL subspecies in a plasma specimen. Using these tools, the role of the intestine in the production of HDL subspecies will be studied. Changes in levels of HDL subspecies will be evaluated during standardized alimentary lipemia, including evaluation of any transitory species that may be formed in the process of chylomicron metabolism. Identification of species absent from the plasma of patients with no functional small bowel will indicate whether certain unique subspecies originate directly of indirectly as a result of intestinal absorption. Similarly, patients with genetic lipoprotein lipase deficiency will be studied to determine whether the lipolysis of chylomicrons is involved in the production of HDL subspecies. Knowledge of th natural speciation of HDL is fundamental to understanding the plurality of roles of those lipoproteins and may be expected to lead to assignment of individual metabolic functions to at least some subspecies. Identification of subspecies that originate directly or indirectly from intestine will be essential for understanding the mechanisms of HDL formation from that source. In turn, such knowledge may lead to modifications of diet that can modulate levels of circulating HDL and perhaps modify the risk of cornary artery disease.
