Dietary cholesterol and differential monocyte chemoattractant protein-1 gene expression in aorta and liver of apo E-deficient mice.

Abstract

In humans, hypercholesterolemia, steatohepatitis, and risk for arteriosclerosis are associated. Apolipoprotein E-deficient mice, a widely used animal model, show both arteriosclerosis and steatohepatitis in response to high-fat and cholesterol diets. We have found a relationship between these conditions and a higher mRNA aortic and hepatic monocyte chemoattractant protein-1 (mcp-1) gene expression. Both tissues respond in a similar way when dietary cholesterol is provided for a few weeks but differently if the conditions persist for a protracted period of time. After 8 months of treatment, the mcp-1 gene expression in the aorta continues increasing but in the liver decreases. This coincides with a significant increase in hepatic ppar-delta anti-inflammatory gene expression. Apparently, the arterial wall cannot prevent the deleterious effects of higher mcp-1 expression by increasing ppar-delta gene expression and the lesion progress. However, in the liver, the activation of anti-inflammatory genes may reduce the hepatic mcp-1 expression which significantly decreases the inflammatory response. This differential inflammatory gene expression in aorta and liver may support the idea that anti-inflammatory transcription factors are involved in the response to diet and inflammation. Therefore, the use of cholesterol-enriched diets should be carefully considered in the apolipoprotein E-deficient mice because they may trigger different stimuli and seriously hinder the interpretation of possible findings.

• Authors: Mònica Tous, Natàlia Ferré, Anna Rull, Judit Marsillach, Blai Coll, Carlos Alonso-Villaverde, Jordi Camps, Jorge Joven
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 340 Issue 4 Pg. 1078-84 (Feb 24 2006) ISSN: 0006-291X [Print] United States
• PMID: 16403442 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins E
• Ccl2 protein, mouse
• Chemokine CCL2
• Cholesterol, Dietary

Topics

• Animals
• Aorta (metabolism)
• Apolipoproteins E (deficiency)
• Atherosclerosis (etiology, metabolism)
• Chemokine CCL2 (metabolism)
• Cholesterol, Dietary (adverse effects, metabolism)
• Fatty Liver (etiology, metabolism)
• Gene Expression Regulation
• Liver (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Organ Specificity
• Tissue Distribution