Oxysterols present in atherosclerotic tissue decrease the expression of lipoprotein lipase messenger RNA in human...

Area of Science:

• Biochemistry
• Cell Biology
• Pathology

Background:

• Oxysterols are cholesterol oxidation products found in atherosclerotic lesions.
• Macrophages are key cells in atherosclerosis, accumulating lipids and becoming foam cells.
• Lipoprotein lipase (LPL) plays a crucial role in lipid metabolism and its regulation is important in atherosclerosis.

Purpose of the Study:

• To investigate the presence and distribution of oxysterols in macrophages from atherosclerotic tissue.
• To determine the effect of different oxysterols on the regulation of lipoprotein lipase (LPL) mRNA expression in macrophages.

Main Methods:

• Isolation of macrophages from human and rabbit atherosclerotic aorta.
• Analysis of oxysterol content using isotope dilution mass spectrometry.
• Incubation of human monocyte-derived macrophages with various oxysterols.
• Quantification of LPL mRNA levels by quantitative RT-PCR.
• Measurement of LPL activity in the cell medium.

Main Results:

• Macrophages from human and rabbit atherosclerotic aorta contained similar oxysterol distributions, with high levels of 27-hydroxycholesterol in human macrophages.
• Incubation with 7 beta-hydroxycholesterol and 25-hydroxycholesterol led to a 70-75% reduction in LPL mRNA in human macrophages.
• LPL activity in the medium was also reduced following exposure to these specific oxysterols.
• Cholesterol and other tested oxysterols did not affect macrophage LPL mRNA expression.

Conclusions:

• Oxysterols accumulate in macrophage-derived foam cells in atherosclerotic aorta.
• Specific oxysterols, 7 beta-hydroxycholesterol and 25-hydroxycholesterol, suppress LPL mRNA expression in human macrophages.
• Oxysterol exposure may contribute to the previously observed low LPL mRNA levels in arterial foam cells.