Open AccessInhibition of Glycosphingolipid Synthesis Induces a Profound Reduction of Plasma Cholesterol and Inhibits Atherosclerosis Development in APOE*3 Leiden and Low-Density Lipoprotein Receptor−/− Mice
Author(s) -
Florence Biétrix,
Elisa Lombardo,
Cindy P. A. A. van Roomen,
Roelof Ottenhoff,
Mariska Vos,
Patrick C.N. Rensen,
Arthur J. Verhoeven,
Johannes M. F. G. Aerts,
Albert K. Groen
Publication year - 2010
Publication title -
arteriosclerosis, thrombosis, and vascular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.007
H-Index - 270
eISSN - 1524-4636
pISSN - 1079-5642
DOI - 10.1161/atvbaha.109.201673
Subject(s) - apolipoprotein e , glycosphingolipid , ldl receptor , chemistry , reduction (mathematics) , endocrinology , low density lipoprotein , medicine , cholesterol , lipoprotein , biochemistry , disease , mathematics , geometry
The iminosugar N-(5'-adamantane-1'-yl-methoxy)-pentyl-1-deoxynoijirimycin (AMP-DNM), an inhibitor of the enzyme glucosylceramide synthase catalyzing glycosphingolipid (GSL) biosynthesis, ameliorates diabetes and reduces liver steatosis in ob/ob mice. Because an accumulation of sphingolipids, including sphingomyelin and GSLs, has been reported in atherosclerotic lesions in animal models and in humans, the objective of this study was to determine whether AMP-DNM also exerts beneficial effects on the development of atherosclerosis.