Abstract
To investigate the metabolic disposition of phosphatidylcholine vesicles, unilamellar vesicles of egg phosphatidylcholine or cholesterol/phosphatidylcholine were injected intravenously into rats. Ten minutes after injection of 0.5 to 3.0 mg phosphatidylcholine vesicles, a major fraction of their radioactivity and mass had been incorporated into high density lipoproteins (HDL). Agarose gel chromatography showed that the phospholipid of vesicles was incorporated into the plasma HDL region, in association with release of a trapped marker, [3H]inulin. Density gradient ultracentrifugtion showed that the highest specific activity of phospholipid was present in HDL of d 1.08-1.12 g/ml, consisting of homogenous spherical particles by negative stain electron microscopy. With increasing cholesterol/phosphatidylcholine ratio of injected vesicles, there was progressively less incorporation of phospholipid into HDL and vesicles retaining [3H]inulin were re-isolated from plasma. Sixty minutes after injection of cholesterol/phosphatidylcholines vesicles, phospholipid appeared to be partly transferred into HDL and partly taken up by the liver. In summary, injection of unilamellar egg phosphatidylcholine vesicles results in a rapid incorporation of vesicle phospholipid into plasma HDL, primarily as a result of insertion of phospholipid into pre-existing HDL. This process is inhibited by a high content of vesicle unesterified cholesterol. These studies may have relevance to the mechanisms of transfer of phosphatidylcholine from chylomicrons into plasma.
Highlights
To investigate the metabolic disposition of phosphatidylcholine vesicles, unilamellar vesicles of egg phosphatidylcholineor cholesterol/phosphatidylcholinewere injected intravenously into rats
Following injection of unilamellar egg yolk phosphatidyl-choline vesicles into the rat, phospholipid radioactivity was incorporated into high density lipoproteins (HDL) [8],suggesting that similar interactions between vesicles and HDL may occur in vivo
The transfer of vesicle phospholipid radioactivity into HDL was inhibited by the presence of unesterified cholesterol in the vesicles
Summary
To investigate the metabolic disposition of phosphatidylcholine vesicles, unilamellar vesicles of egg phosphatidylcholineor cholesterol/phosphatidylcholinewere injected intravenously into rats. Injection of unilamellar egg phosphatidylcholine vesicles results in a rapid incorporation of vesicle phospholipid into plasma HDL, primarily as a result of insertion of phospholipid into pre-existing HDL. This process is inhibited by a high content of vesicle unesterified cholesterol. Reports from several laboratories [9,10,11,12] indicate that, at least in the presence of higher cholesterol contents, solubilization of phospholipid by apoA-I is markedly inhibited, and the resulting lipoprotein recombinants are relatively cholesterol-poor These studies raise the possibility that interactions between phospholipid vesicles and intact plasma HDL may be modified by the presence of unesterified cholesterol in the phospholipid vesicles. T h e aims of these experiments were 1) to determine whether phospholipid mass would be incorporated into HDL in vivo; 2) to examine the mechanisms of uptake of phospholipid by HDL, and 3) to investigate the effect of variable vesicle cholesterol/phospholipid ratio on this process
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