Abstract |
Reduction of plasma LCAT activity has been observed in several conditions in which the size of HDL particles is increased; however, the mechanism of this reduction remains elusive. We investigated the plasma activity, mass, and in vivo catabolism of LCAT and its association with HDL particles in human apolipoprotein A-I transgenic, scavenger receptor class B type I knockout (hA-ITg SR-BI-/-) mice. Compared with hA-ITg mice, hA-ITg SR-BI-/- mice had a 4-fold higher total plasma cholesterol concentration, which occurred predominantly in 13-18 nm diameter HDL particles, a significant reduction in plasma esterified cholesterol-total cholesterol (EC/TC) ratio, and significantly lower plasma LCAT activity, suggesting a decrease in LCAT protein. However, LCAT protein in plasma, hepatic mRNA for LCAT, and in vivo turnover of 35S-radiolabeled LCAT were similar in both genotypes of mice. HDL from hA-ITg SR-BI-/- mice was enriched in sphingomyelin (SM), relative to phosphatidylcholine, and had less associated [35S]LCAT radiolabel and endogenous LCAT activity compared with HDL from hA-ITg mice. We conclude that the decreased EC/TC ratio in the plasma of hA-ITg SR-BI-/- mice is attributed to a reduction in LCAT reactivity with SM-enriched HDL particles.
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Authors | Ji-Young Lee, Robert M Badeau, Anny Mulya, Elena Boudyguina, Abraham K Gebre, Thomas L Smith, John S Parks |
Journal | Journal of lipid research
(J Lipid Res)
Vol. 48
Issue 5
Pg. 1052-61
(May 2007)
ISSN: 0022-2275 [Print] United States |
PMID | 17272829
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Apolipoprotein A-I
- CD36 Antigens
- Lipids
- RNA, Messenger
- Phosphatidylcholine-Sterol O-Acyltransferase
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Topics |
- Animals
- Apolipoprotein A-I
(genetics, metabolism)
- CD36 Antigens
(genetics, metabolism)
- Humans
- Lecithin Cholesterol Acyltransferase Deficiency
(genetics, metabolism)
- Lipids
(blood)
- Liver
(metabolism)
- Mice
- Mice, Knockout
- Phosphatidylcholine-Sterol O-Acyltransferase
(genetics, metabolism)
- RNA, Messenger
(genetics)
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