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 Courtney, Henry J. Pownall

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 1 2011

Fingerprint

Apolipoproteins
LDL Receptors
HDL Cholesterol
Apolipoproteins E
Cholesterol Esters
Liver
Cholesterol
Injections
Apolipoprotein A-I
HDL Lipoproteins
Lipids
opacity factor
Inbred C57BL Mouse

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

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

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 31, No. 8, 01.08.2011, p. 1834-1841.

Research output: Contribution to journalArticle

@article{989bcc7fdb354583a77584404038576a,
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). 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.",
author = "Corina Rosales and Daming Tang and Gillard, {Baiba K.} and Harry Courtney and Pownall, {Henry J.}",
year = "2011",
month = "8",
day = "1",
doi = "10.1161/ATVBAHA.111.224360",
language = "English (US)",
volume = "31",
pages = "1834--1841",
journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",
issn = "1079-5642",
publisher = "Lippincott Williams and Wilkins",
number = "8",

}

TY - JOUR

T1 - 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

AU - Rosales, Corina

AU - Tang, Daming

AU - Gillard, Baiba K.

AU - Courtney, Harry

AU - Pownall, Henry J.

PY - 2011/8/1

Y1 - 2011/8/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=80051552226&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80051552226&partnerID=8YFLogxK

U2 - 10.1161/ATVBAHA.111.224360

DO - 10.1161/ATVBAHA.111.224360

M3 - Article

VL - 31

SP - 1834

EP - 1841

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

IS - 8

ER -