The influence of lipolytic enzymes and lipid transfer proteins on the fate of very low-density lipoprotein and high-density lipoprotein constituents.
Date
1992
Authors
Murdoch, Susan Jane.
Journal Title
Journal ISSN
Volume Title
Publisher
Dalhousie University
Abstract
Description
The process of the conversion of triglyceride-rich lipoproteins to low density lipoprotein (LDL) and high density lipoprotein (HDL) is considered central to an understanding of the positive association of intermediate density (IDL) and LDL with the development of atherosclerosis and the apparent protective effect of HDL. The conversion process is thought to involve lipolytic enzymes and the lipid transfer proteins in the vascular compartment.
The purpose of this study was to investigate in vitro the role of lipoprotein lipase, hepatic lipase and the lipid transfer proteins in the metabolism of VLDL in the presence of HDL. The results of the in vitro incubations were compared to those observed in vivo as a result of heparin-induced lipolysis in normolipidemic subjects.
The metabolism of VLDL by lipoprotein lipase resulted in 88-94% hydrolysis of the triglycerides and 30% hydrolysis of the phospholipids of VLDL. The transfer of apo CII and CIII from VLDL to HDL was extensive (88-100%) while the apo E transfer was substantially lower (30%). Unesterified cholesterol and phospholipid were transferred to HDL and in some experiments there was a transfer of cholesteryl ester from VLDL to the HDL region. The transfer of cholesteryl ester was accompanied by an increased transfer of phospholipid from VLDL to the HDL. The metabolized VLDL did not form typical plasma LDL since the particles were considerably larger, less dense, contained a significant amount of apo E and had a very high surface to core ratio.
The addition of hepatic lipase to the lipoprotein lipase incubation had little effect on VLDL conversion to LDL but caused an extensive hydrolysis of HDL triglycerides.
The addition of the lipid transfer proteins to the lipoprotein lipase incubation increased the transfer of unesterified cholesterol, phospholipid and apo E from VLDL to HDL by 1.5 to 2 fold. Net phospholipid transfer activity to HDL was increased while net cholesteryl ester transfer activity from HDL to VLDL was decreased in the presence of lipoprotein lipase. The metabolized VLDL particles were more like plasma LDL than those produced by lipoprotein lipase alone since the particles contained less apo E, had a lower surface to core ratio and approached LDL size.
The in vivo studies of heparin-induced lipolysis yielded results that were similar to those observed in vitro when the combined effects of lipoprotein lipase, hepatic lipase and the lipid transfer proteins were considered.
It is concluded that lipoprotein lipase and the lipid transfer proteins are the most important factors for the conversion of plasma VLDL to LDL with an associated accumulation of lipid and apoprotein mass in HDL.
Thesis (Ph.D.)--Dalhousie University (Canada), 1992.
The purpose of this study was to investigate in vitro the role of lipoprotein lipase, hepatic lipase and the lipid transfer proteins in the metabolism of VLDL in the presence of HDL. The results of the in vitro incubations were compared to those observed in vivo as a result of heparin-induced lipolysis in normolipidemic subjects.
The metabolism of VLDL by lipoprotein lipase resulted in 88-94% hydrolysis of the triglycerides and 30% hydrolysis of the phospholipids of VLDL. The transfer of apo CII and CIII from VLDL to HDL was extensive (88-100%) while the apo E transfer was substantially lower (30%). Unesterified cholesterol and phospholipid were transferred to HDL and in some experiments there was a transfer of cholesteryl ester from VLDL to the HDL region. The transfer of cholesteryl ester was accompanied by an increased transfer of phospholipid from VLDL to the HDL. The metabolized VLDL did not form typical plasma LDL since the particles were considerably larger, less dense, contained a significant amount of apo E and had a very high surface to core ratio.
The addition of hepatic lipase to the lipoprotein lipase incubation had little effect on VLDL conversion to LDL but caused an extensive hydrolysis of HDL triglycerides.
The addition of the lipid transfer proteins to the lipoprotein lipase incubation increased the transfer of unesterified cholesterol, phospholipid and apo E from VLDL to HDL by 1.5 to 2 fold. Net phospholipid transfer activity to HDL was increased while net cholesteryl ester transfer activity from HDL to VLDL was decreased in the presence of lipoprotein lipase. The metabolized VLDL particles were more like plasma LDL than those produced by lipoprotein lipase alone since the particles contained less apo E, had a lower surface to core ratio and approached LDL size.
The in vivo studies of heparin-induced lipolysis yielded results that were similar to those observed in vitro when the combined effects of lipoprotein lipase, hepatic lipase and the lipid transfer proteins were considered.
It is concluded that lipoprotein lipase and the lipid transfer proteins are the most important factors for the conversion of plasma VLDL to LDL with an associated accumulation of lipid and apoprotein mass in HDL.
Thesis (Ph.D.)--Dalhousie University (Canada), 1992.
Keywords
Chemistry, Biochemistry., Health Sciences, Pathology.