NATURE OF NASCENT HEPATIC HDL IN THE PRIMATE

Project: Research project

Project Details

Description

High density lipoproteins (HDL) are lipid-protein complexes found in the
circulation, that play vital roles in lipid transport. They have been the
focus of much interest because of the finding that their concentration in
the blood correlates inversely with the risk of atherosclerotic vascular
disease. Hence, there is an urgent need to understand how HDL enters and
leaves the circulation. This application is aimed at identifying the
nature of HDL released by the liver, which together with the intestine is a
major site of HDL production. Current evidence suggests that nascent HDL
is secreted by the liver in an immature form and is then modified in the
circulation to produce a "mature" HDL particle. By understanding this
process one can begin to ask meaningful questions about how it is
regulated, how it may be disturbed and what the consequences would be for
HDL metabolism and lipid transport.

Since nascent HDL precursors are not identifiable in normal serum or plasma
the research plan calls for the collection of this material in a liver
perfusion system. The baboon liver has been chosen for this purpose
because of the similarity between the HDL of this animal and that of man.

Perfusion media and liver homogenates will be analyzed by gel-filtration
and density gradient ultracentrifugation and the distribution of nascent
HDL determined using sensitive, specific radioimmunoassays for the two
major HDL peptides or apoproteins, apo A-I and apo A-II. Newly-synthesized
apoprotein will be recognized by isoelectric focusing and by the
invorporation of radioactive tracers.

Characterization and isolation of nascent hepatic HDL will be followed by
in vitro studies of its maturation. A systematic approach in which nascent
particles are incubated with various plasma factors considered to be
potentially important in HDL assembly will identify the critical components
of this process.
StatusFinished
Effective start/end date12/31/8912/31/89

Funding

  • National Heart, Lung, and Blood Institute

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