Title: Adenoviral low density lipoprotein receptor attenuates progression of atherosclerosis and decreases tissue cholesterol levels in a murine model of familial hypercholesterolemia
Authors: Jacobs, Frank
Van Craeyveld, Eline
Feng, Yingmei
Snoeys, Jan
De Geest, Bart # ×
Issue Date: Dec-2008
Publisher: Elsevier
Series Title: Atherosclerosis vol:201 issue:2 pages:289-297
Abstract: Familial hypercholesterolemia is an autosomal codominant disease characterized by high concentrations of pro-atherogenic lipoproteins and premature atherosclerosis secondary to low-density lipoprotein receptor (LDLr) deficiency. In the current study, the effects of gene transfer with 5 x 10ee10 particles of E1E3E4-deleted adenoviral vectors expressing the LDLr (AdLDLr) or VLDLr (AdVLDLr) under control of the hepatocyte-specific human a1-antitrypsin promoter and 4 copies of the human apo E enhancer in C57BL/6 LDLr-/- mice were investigated. Evaluation was performed in both sexes and in mice fed either standard chow or an atherogenic diet containing 0.2% cholesterol and 10% coconut oil. Compared to control mice, AdLDLr and AdVLDLr persistently decreased plasma non-HDL cholesterol in both sexes and on both diets. Six months after LDLr gene transfer in mice fed the atherogenic diet, average intimal area was 2.5-fold (p<0.01) and 3.2-fold (p<0.001) lower in male and female mice, respectively, compared to controls. In mice fed standard chow, intimal area was reduced 22-fold (p<0.001) and 21-fold (p<0.001) after LDLr gene transfer in male and female mice, respectively. We show that non-HDL lipoproteins are more atherogenic in female mice, independent of sex differences of plasma HDL cholesterol levels, and that saturated fat does not have an effect on atherosclerosis independent of plasma cholesterol levels. Finally, quantification of tissue cholesterol levels indicates that AdLDLr does not induce cholesterol accumulation in the liver and reduces cholesterol content in the myocardium, quadriceps muscle and kidney. In conclusion, hepatocyte-specific LDLr gene transfer significantly improves cholesterol homeostasis in LDLr-/- mice.
ISSN: 0021-9150
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science