STUDY OF AGE RELATED HYPERLIPIDEMIA IN RATS

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.