| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1991: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1990: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
(1). Two species of lipoprotein containing apoA-I, one containing only apoa-l(LpA-I), and the other containing apoA-I and apoA-II(LpA-I/A-II), were tested for their effects on macrophage fawn cells. Rat macrophages were converted to foam cells by incubation with radiolabelled acetylated LDL. Incubation with LpA-I or LpA-I/A-II decreased the cellular cholesterol esters(CE)mass. However, the free cholesterol(FC)mass was only reduced by LPA-I. All the radioactivity excreted into the medium was associated with LpA-I or LpA-I/A-II ; 39 % of the excreted radioactivity was esteritied in LpA-I and 10 % in LpA-I/A-II. Upon complete inactivation of lecithin : cholesterol acyltransferase(LCAT)activity with dithiobisnitrobenzoic acid, the cholesterol reducing capacity of LpA-I was weakened significantly. However, the CE mass reducing capacity of LpA-I/A-II was not affected. When LpA-I and LpA-I/A-Il were combined, the cholesterol reducing capacity of the mixture was similar to that of LpA-I alone.
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However, LpA-I re-isolated from the medium showed a lower esterification rate than did the re-isolated LpA-I/A-II, thereby indicating that the cholesterol esterified in LpA-I was transferred to LpA-I/A-II. These results suggest that(i)the function of LpA-I is closely linked to the LCAT activity while that of LpA-I/A-II is not, and(ii)LpA-I in concert with LpA-I/A-II induces a series of extracellular events ; LCAT-mediated estefification of excreted FC by LpA-I and a subsequent CE transfer to LpA-I/A-II. These mechanisms might be important for net cholesterol efflux from macrophage foam cells in physiological states.
(2)We investigated the postprandial changes of two species of lipoproteins containing apoA-I : lipoprotein containing apoA-I but no apoA-II(LpA-I), and lipoprotein containing apoA-I and apoA-II(LpA-I/A-II). These lipoproteins were isolated from 10men and 11women at 0, 4 and 6 hr after eating butter. In LPA-I, the levels of all lipids except triglyceride were increased at 4 and 6 hr in the women. In the men, all lipids were increased only at 4 hr. The increase of apoA-I level was found at 6 hr only in the women. In LpA-I/A-II, the levels of all lipids were increased at 4 hr and only phospholipid(PL)was increased at 6 hr in the women. In the men, free cholesterol and PL were increased at 4 and 6 hr. The increases of apoA-I and apoA-II levels were found at 4 and 6 hr only in the men. These results suggest that the postprandial changes are gender-related and these may relate to the different incidence of atheroscierotic cardiovascular disorders. Less
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