Abstract 326: Streptococcal Serum Opacity Factor Product, Cholesteryl Ester Rich Particles, Induce Cholesterol Ester Metabolism and Bile Acid Secretion after Uptake by Human Huh7 Hepatocytes

Plasma concentrations of HDL-cholesterol (C) negatively correlate with atherosclerotic cardiovascular disease. Nevertheless, current evidence suggests that this correlation is not axiomatic and that some forms of HDL are dysfunctional and atherogenic. Interventions that raise HDL-C have not been uniformly successful suggesting that mechanisms by which HDL-C is increased determine its anti atherogenic potency. Additionally, mice overexpressing the HDL receptor, SR-BI, have lower plasma HDL-C levels and less atherosclerosis. Thus, new strategies that reduce HDL-C while promoting reverse cholesterol transport (RCT) may have therapeutic value. Serum opacity factor (SOF) disrupts HDL and forms three products, including a cholesteryl ester-rich microemulsion (CERM) containing apo E and the CE of ~400,000 HDL particles. Hepatic CE uptake in Huh7 cells is faster when delivered by CERM than by HDL, and cleared both in vitro and in vivo, in part, via the LDL-receptor (LDLR). We investigated the therapeutic potentia...