apoE-rich HDL1 in the rat: effects of lipid transfer protein

In this study we determined in vivo conversions of human ’H-labeled cholesteryl ester-labeled HDL3 ([’HICEHDLs) in male rats and the effects of partially purified lipid transfer protein on the conversion processes. Zonal centrifugation techniques were used to prepare the [’HICE-HDLS and to follow the conversion processes. One hour after the injection, a complete conversion of HDLs to and HDL,-density species was found. With time, [’HICE separated with apoE-rich HDLl and, by 18 hr, 35.9% of plasma radioactivity was associated with the a oE rich HDL, lipoprotein fraction. In vitro incubation of HDLs+HDLZ conversion, but no movement of radioactivity to HDLI was observed. Injection of the rats with partially purified lipid transfer proteins induced [ ’HICE exchange between lipoproteins. The conversion of HDLs to HDL2, however, was minimally affected. Formation of [’H]CE-HDL1, in contrast, was reduced to about one-half of that found in control animals.m It is concluded that in vivo conditions are necessary for conversions of HDLS (and HDL,) to HDL1, and that lipid transfer reactions delay this process.-Gavish, D., Y. Oschry, and S. Eisenberg. In vivo conversion of human HDLs to HDL, and apoE-rich HDL, in the rat: effects of lipid transfer protein. J. [ % HICE-HDLS in rat plasma reproduced in part the Lipid RLS. 1987. 28: 257-267. Supplementary key w o r d s cholesteryl estem 1ecithin:cholesterol acyltransferase low density lipoprotein In recent years it has become apparent that several metabolic reactions participate in processes that regulate HDL levels and subpopulation distribution (1). It has been suggested that supply of free cholesterol and phospholipid (from lipolyzed and intact lipoproteins and from cell membranes) followed by cholesterol esterification causes conversion of small-sized and heavy HDL particles (e.g., HDL3), to large-sized and less dense particles (e.g., HDL2) (2-5). Another set of metabolic reactions appears to cause “reverse conversion” of HDL, i.e., formation of HDL3 from HDLp (1, 2, 6, 7). Activity of the plasma lipid transfer proteins (814) seems to be essential for the “reverse conversion” reaction, possibly acting in concert with the hepatic lipase (1, 6, 7, 15, 16). More recently, it has been proposed that the apoE-rich HDL, population, an HDL present normally in rats (17-20), also participates in the HDL conversion-“reverse conversion” reactions (1). According to this view, excessive accumulation of cholesteryl esters in HDLB (21), or perhaps even HDL3 (22), results in conversion of apoA-1rich HDL2 (or HDL3) to apoE-rich HDL,. Whether lipid transfer proteins cause a “reverse conversion” of HDLl is not known. HDL conversions and “reverse conversions” can be conveniently studied in the rat, an animal species whose plasma lacks lipid transfer activity (10, 19). When injected with [ 3H]cholesteryl ester-labeled lipoproteins, movement of the radioactive molecule between HDL populations would indicate conversion of the whole lipoprotein particle. When such animals are treated with lipid transfer proteins, effects of “reverse conversion” could presumably be identified. These considerations led us to initiate an investigation of human HDL3 conversions in rats and the effects of injected lipid transfer proteins on the conversion process. Because the injected HDL3 was devoid of apoE, the investigation was particularly relevant to events that regulate the formation of apoE-rich HDL1. The study indeed demonstrated that HDL3 is a precursor of HDL2 and of apoE-rich HDL1, and that lipid transfer proteins delay the conversion process, especially to HDLl.