Literature DB >> 9851961

Severe atherosclerosis and hypoalphalipoproteinemia in the staggerer mouse, a mutant of the nuclear receptor RORalpha.

A Mamontova1, S Séguret-Macé, B Esposito, C Chaniale, M Bouly, N Delhaye-Bouchaud, G Luc, B Staels, N Duverger, J Mariani, A Tedgui.   

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.

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Year:  1998        PMID: 9851961     DOI: 10.1161/01.cir.98.24.2738

Source DB:  PubMed          Journal:  Circulation        ISSN: 0009-7322            Impact factor:   29.690


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