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

Corina Rosales, Daming Tang, Baiba K. Gillard, Harry S. Courtney, Henry J. Pownall

Research output: Contribution to journalArticle

15 Scopus citations

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). Methods and 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%, t1/2=44±18 minutes) whereas control saline injections had a negligible effect. Similar experiments with apoE and LDLR mice reduced plasma total cholesterol0% 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%. Conclusion-: 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.

Original languageEnglish (US)
Pages (from-to)1834-1841
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume31
Issue number8
DOIs
StatePublished - Aug 2011

Keywords

  • atherosclerosis
  • lipids
  • lipoproteins
  • pharmacokinetics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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