title: 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: OBJECTIVE
  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).
  
  
  RESULTS
  rSOF (4 μg) 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 μg 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%.
  
  
  CONCLUSIONS
  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.
authors: Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
authors: Corina
authors: C
authors: Rosales
authors: Daming
authors: D
authors: Tang
authors: Baiba K
authors: BK
authors: Gillard
authors: Harry S
authors: HS
authors: Courtney
authors: Henry J
authors: HJ
authors: Pownall
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