Abstract
Background:
Hypoalphalipoproteinemia is the most common lipoprotein abnormality in patients with coronary artery disease, yet its causes are unknown.
Methods and results:
We show that the homozygous staggerer (sg/sg) mutant mouse, which carries a deletion within the nuclear receptor RORalpha gene, develops severe atherosclerosis when maintained on an atherogenic diet. In addition, sg/sg mice display a profound hypoalphalipoproteinemia, which is associated with decreased plasma levels of the major HDL proteins, apolipoprotein (apo) A-I and apoA-II. This decrease in HDL levels in sg/sg mice is due to lowered apoA-I gene expression in the intestine but not in the liver. ApoA-II gene expression is unaffected.
Conclusions:
These results suggest that the RORalpha gene contributes to the plasma HDL level and susceptibility to atherosclerosis.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Aorta / pathology
-
Apolipoprotein A-I / blood
-
Apolipoprotein A-I / genetics
-
Apolipoprotein A-I / metabolism
-
Apolipoprotein A-II / blood
-
Apolipoprotein A-II / genetics
-
Arteriosclerosis / genetics*
-
Arteriosclerosis / pathology
-
Arteriosclerosis / physiopathology*
-
Body Weight
-
Cholesterol / blood
-
Cholesterol, HDL / blood
-
Diet, Atherogenic
-
Female
-
Gene Deletion
-
Intestinal Mucosa / metabolism
-
Lipoproteins, HDL / blood*
-
Lipoproteins, HDL / deficiency*
-
Liver / metabolism
-
Male
-
Mice
-
Mice, Inbred C57BL
-
Mice, Neurologic Mutants
-
Nerve Tissue Proteins / genetics
-
Nuclear Receptor Subfamily 1, Group F, Member 1
-
RNA, Messenger / biosynthesis
-
Receptors, Cytoplasmic and Nuclear / genetics*
-
Trans-Activators / genetics*
Substances
-
Apolipoprotein A-I
-
Apolipoprotein A-II
-
Cholesterol, HDL
-
Lipoproteins, HDL
-
Nerve Tissue Proteins
-
Nuclear Receptor Subfamily 1, Group F, Member 1
-
RNA, Messenger
-
Receptors, Cytoplasmic and Nuclear
-
Trans-Activators
-
Cholesterol