Prolonged lipoprotein half-life: effect on oxidative stability and physical features of lipoprotein particles

Abstract

Atherosclerotic cardiovascular disease (ASCVD) is responsible for two out of the three leading causes of death in the United States. Oxidatively modified apolipoprotein B-containing lipoprotein (apoB-LPs) are known to contribute to atherosclerotic lesion formation. Based on separate studies, small, dense LDL (apoB-LPs) with longer half-lives have proven to be more susceptible to oxidative modification. The primary purpose of this investigation was to determine: 1) whether the yolk-specific very-low-density lipoprotein (VLDLy) have smaller diameters in Restricted Ovulator (R/O) hens where apoB-LP clearance is delayed by apoB-LP receptor dysfunction compared to sister hens with normal ovarian function 2) whether, in this same model, changes in the relative amounts of lipoprotein density classes of VLDL, LDL, and high density lipoproteins (HDL) occur in accordance with effects observed in mammalian models of delayed LDL clearance such as the LDL-receptor knockout mouse that is also known to experience prolonged circulation and continued intravascular metabolism and, 3) whether delayed apoB-LP clearance results in increased particle susceptibility to oxidation under conditions of relatively high plasma estrogen. No significant difference was found between the VLDLy diameters collected from twenty-three sexually mature R/O and twenty-nine normal (NOR) laying sister hens. The composition of VLDL and LDL fractions significantly differed in total plasma C and triacylglyceride between R/O and NOR hens, indicating continued intravascular metabolism for VLDLy in R/O hens. Oxidative susceptibility of VLDLy was measured by conjugated diene and hexanal formation under copper ion exposure. The initiation and propagation of conjugated diene formation was significantly faster (P < 0.05) for VLDLy isolated from the R/O hens when compared to VLDLy isolated from the NOR hens. The R/O VLDLy particles produced significantly (P < 0.05) greater amounts of hexanal than the NOR particles for the first five hours of incubation with copper. These findings demonstrate that lipoprotein susceptibility to oxidation is highly dependent on particle age. Thus, any treatment to reduce apo B-LP concentration, an indirect measure of apoB-LP clearance rate, would also reduce apo B-LP age and ASCVD risk.