The effect of lipoprotein structure on interlipoprotein lipid transfers by cholesteryl ester transfer protein.

Abstract

Alterations in low density lipoprotein (LDL) and high density lipoprotein (HDL) composition that occur in dyslipidemic states may modulate a number of events involved in cholesterol homeostasis. To elucidate the details involved, the relationship between lipoprotein structural properties and cholesteryl ester transfer protein (CETP) mediated neutral lipid exchange has been studied in native lipoproteins, reconstituted apoB (LpB) and homogeneous, recombinant HDL (Lp2A-I) particles containing palmitoyloleoyl phosphatidylcholine (POPC), cholesteryl linoleate (CE) and phosphatidyl inositol (PI). Decreasing the POPC content of Lp2A-I particles, from 150 to 70 molecules/particle confers a small change in surface potential, a decrease in thermodynamic stability and increases CE mass transfer from LDL to Lp2A-I by 30%. Increasing the PI content in Lp2A-I from 0 to 16 molecules/particle increases the surface potential, decreases the thermodynamic stability and significantly increases CE mass transfer to Lp2A-I by 22%. In general, the rates of CE transfer from LDL to Lp2A-I were over 100-fold greater than in the opposite direction. CETP mediated transfer of free cholesterol (FC) from LDL into Lp2A-I was unaffected by changes in Lp2A-I POPC content, while increases in PI content increased FC transfer into Lp2A-I by 40%. Inclusion of 90 molecules of PI into reconstituted LDL (LpB) affected net CE and triacylglycerol (TG) mass transfer to native HDL (nHDL). Addition of PI to LpB essentially abolished the net CE mass transfer from LpB to nHDL. The direction of transfer of TG from LpB to HDL was reversed by the addition of PI. Incubation of PI with plasma caused a decrease in the net mass of CE, TG and FC in apoB-containing lipoproteins. Decreasing the POPC content in Lp2A-I particles significantly decreases the particle stability. Addition of PI directly increases the particle charge, and also decreases particle stability. (Abstract shortened by UMI.)