Apolipoprotein E mediates enhanced plasma high-density lipoprotein cholesterol clearance by low-dose streptococcal serum opacity factor via hepatic low-density lipoprotein receptors in vivo.

ABSTRACT: Recombinant streptococcal serum opacity factor (rSOF) mediates the in vitro disassembly of human plasma high-density lipoprotein (HDL) into lipid-free apolipoprotein (apo) A-I, a neo-HDL that is cholesterol poor, and a cholesteryl ester-rich microemulsion (CERM) containing apoE. Given the occurrence of apoE on the CERM, we tested the hypothesis that rSOF injection into mice would reduce total plasma cholesterol clearance via apoE-dependent hepatic low-density lipoprotein receptors (LDLR).rSOF (4 ?g) injection into wild-type C57BL/6J mice formed neo-HDL, CERM, and lipid-free apoA-I, as observed in vitro, and reduced plasma total cholesterol (-43%, t(1/2)=44±18 minutes) whereas control saline injections had a negligible effect. Similar experiments with apoE(-/-) and LDLR(-/-) mice reduced plasma total cholesterol ?0% and 20%, respectively. rSOF was potent; injection of 0.18 ?g of rSOF produced 50% of maximum reduction of plasma cholesterol 3 hours postinjection, corresponding to a ?0.5-mg human dose. Most cholesterol was cleared hepatically (>99%), with rSOF treatment increasing clearance by 65%.rSOF injection into mice formed a CERM that was cleared via hepatic LDLR that recognize apoE. This reaction could provide an alternative mechanism for reverse cholesterol transport.

SUBMITTER: Rosales C 

PROVIDER: S-EPMC6032982 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature