Transfer Of Cholesterol Among The Serum Lipoproteins (cholesteryl Ester Transfer, Apoproteins, Uremia)
Date of Award
Doctor of Philosophy (Ph.D.)
Biochemistry and Molecular Biology
Changes in serum lipoproteins and subfractions resulting from the transfer of cholesteryl esters were examined. Incubation of human serum decreased the content of free and esterified cholesterol in HDL and increased cholesteryl esters in the VLDL and LDL. VLDL and LDL were separated by particle size using gel permeation chromatography, and the fractions were found to accept cholesteryl esters from HDL equally well. However, larger LDL particles had greater capacity to accept cholesterol from HDL than did smaller LDL particles.Gel permeation chromatography was used to study the redistribution of cholesterol among the lipoproteins. After incubation, the majority of the transferred cholesteryl esters were found associated with VLDL. During the incubation, in addition to cholesterol and apoproteins A-I and E, redistribution of other lipids was also observed.Incubation of serum resulted in the formation of a lipoprotein particle which exhibited -2 mobility on agarose gel electrophoresis and appeared to be a subspecies of HDL enriched in apo E. These results were confirmed by gel permeation chromatography in which apo E was found to shift to larger particles after the incubation of HDL, in the presence or absence of other lipoproteins.Optimum conditions for the determination of the rate of cholesterol transfer (RCT) were established. Using the method, patients with chronic renal failure were found to have lower RCT values than control subjects (1.85 (+OR-) 1.29 versus 4.83 (+OR-) 2.13 mg cholesterol transferred per 100 ml serum per hour, respectively). Further studies revealed that the cholesterol acceptors (VLDl and LDL) were not defective, and could accept cholesterol in excess of the amount provided by the patients cholesterol donor fraction (containing HDL). The defect was found to reside in the lipoprotein deficient serum fraction (LPD). Although LCAT activities were normal in the serum of the patients, the activity of the cholesteryl ester transfer protein (CETP) was found to be low in patient LPD. Separation of CETP and CETP-inhibitor revealed increased inhibitor activity in the patient LPD as compared to controls. These results indicate that increased inhibitor activity in the patient's serum could be responsible for the low RCT.
Mendez, Armando J., "Transfer Of Cholesterol Among The Serum Lipoproteins (cholesteryl Ester Transfer, Apoproteins, Uremia)" (1986). Dissertations from ProQuest. 1611.