DESCRIPTION:

QTL associated with plasma plant sterol 1b. The confidence interval is Chr14:54729500-122065662 bp,+strand

LABEL:

QTL-Plast1b-Mouse-Chr 14

SCORE TYPE:

Binary

DATE ADDED:

2012-04-02

DATE UPDATED:

2024-10-22

SPECIES:

URI:

http://www.informatics.jax.org/searches/accession_report.cgi?id=MGI:3703625

AUTHORS:

Greenberg ME, Smith JD, Sehayek E

TITLE:

Moderately decreased cholesterol absorption rates are associated with a large atheroprotective effect.

JOURNAL:

Arteriosclerosis, thrombosis, and vascular biology Nov 2009, Vol 29, pp. 1745-50

ABSTRACT:

Human treatment with ezetimibe results in a moderate 50% to 54% decrease in cholesterol absorption and a 15% to 20% decrease in plasma LDL-cholesterol levels; nevertheless, the efficacy of ezetimibe therapy has been recently challenged by the ENHANCE trial. We examined the efficacy of a moderate decrease in cholesterol absorption in preventing atherosclerosis formation in the mouse.Congenic 14DKK animals, consisting of a castaneus (CASA/Rk) chromosome 14 interval introgressed onto the C57BL/6J background, displayed a moderate decrease in cholesterol absorption rates. The effect of moderately decreased absorption on atherosclerosis formation was determined in 14DKK apolipoprotein E knockouts (14DKK-apoEKO). When compared to chow diet-fed control apoEKO mice, congenic 14DKK-apoEKO displayed a moderate 41% decrease in cholesterol absorption rates, 30% to 37% decrease in plasma cholesterol levels, and a 70% decrease in atherosclerosis formation. Studies on cholesterol efflux and reverse cholesterol transport (RCT) from 14DKK bone marrow-derived macrophages rejected a 14DKK interval-dependent atheroprotective effects that operate in macrophages. In contrast, 14DKK-apoEKO congenics were characterized by a 60% increase in RCT from peripheral tissue macrophages.These studies strongly suggest that moderately decreased cholesterol absorption rates result in a large atheroprotective effect attributable to a decrease in plasma cholesterol levels and an increase in RCT from peripheral tissue macrophages. PUBMED: 19661480
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