Studies of esterified cholesterol in sub-fractions of plasma high density lipoproteins

With human lipoproteins and lipoprotein-free plasma incubated at 37 degrees C as a source of esterified cholesterol transfer activity, there was a molecular exchange of esterified cholesterol between the high density lipoprotein (HDL) subfractions, HDL2 (density 1.063-1.125 g/ml) and HDL3 (density 1.125-1.21 g/ml). A transfer of esterified cholesterol from both HDL2 and HDL3 to very low density lipoproteins (VLDL) was also observed. When human plasma was incubated with [3H]cholesterol at 37 degrees C, the newly formed esterified [3H]cholesterol became distributed among all plasma lipoprotein fractions. After 24 h the relative specific activities of esterified cholesterol in HDL3, HDL2, low density lipoproteins (LDL) and VLDL were 1.0, 0.81, 0.77 and 0.79, respectively. In comparable 24-h incubations of the plasma of pigs, a species found to have a very low level of plasma esterified cholesterol transfer activity, the relative esterified cholesterol specific activities in HDL3, HDL2, LDL and VLDL were 1.0, 0.31, 0.12 and 0.01, respectively. However, the addition of rabbit lipoprotein-free plasma as a source of exogenous esterified cholesterol transfer activity to incubations of pig lipoproteins resulted in a distribution of the newly formed esterified [3H]cholesterol which was very similar to that in incubated human plasma. It has been concluded that the formation of plasma esterified cholesterol occurs in the HDL3 subfraction. In man, who possesses adequate levels of esterified cholesterol transfer activity, the esterified cholesterol so formed becomes distributed among all plasma lipoprotein fractions. In pigs, however, which lack transfer activity, the esterified cholesterol formed in HDL3 is only minimally transferred to other fractions and remains predominantly in HDL, resulting in an increase in the HDL particle size with a consequent conversion of HDL3 to the larger HDL2.