Project Details


Age related hyperlipidemia has been reported for both man and rat.
However, the pathophysiology and biochemistry of this process has not yet
been elucidated. The most intriguing phase of vascular lipid transport and
other mechanisms involved with hyperlipidemia is reverse cholesterol
transport or the return of peripheral cholesterol to the liver for
disposal. High density lipoproteins (HDL) and the enzyme
Lecithin:cholesterol acyltransferase (LCAT) have been jointly implicated in
this reverse cholesterol transport pathway. During preliminary studies,
data has been collected that consistently showed an age related decrease in
the fractional rate of cholesterol esterification; a parameter related to
LCAT substrate efficiency and cholesterol ester turnover. Experiments are
proposed to explore the mechanism of age related hyperlipidemia in the rat,
with particular focus on the role of HDL and LCAT. Specific phases of the
project include, 1) Development of an immunoassay procedure for LCAT in
the rat. 2) Refinement of the time course of age related changes in the
rat by studying the specific parameters of plasma lipid metabolism in 12,
15, 18, 21 and 24 month old animals. 3) Study of the age related changes
in the composition of the subfractions of HDL, postulated to serve as
substrates for LCAT in vivo. 4) Study the age related changes that might
occur in the secretion of LCAT from the liver. It is recognized that the
hyperlipidemia observed in senescent animals is probably not directly
related to the aging process but rather it is a secondary or tertiary
development. However, the elucidation of the pathophysiology involved in
age related hyperlipidemia should help in identifying the basic mechanisms
involved in the aging of mammals.
Effective start/end date19/04/8530/06/85