Expression and synthesis of TGF β 1 is induced in macrophages by 9‐oxononanoyl cholesterol, a major cholesteryl ester oxidation product

Abstract Within the broad variety of compounds generated via oxidative reactions in low density lipoproteins (LDL) and subsequently found in the atherosclerotic plaque, are aldehydes still esterified to the parent lipid and termed core‐aldehydes. The most represented cholesterol core‐aldehyde in LDL...

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Published in:BioFactors (Oxford) 2005-01, Vol.24 (1-4), p.209-216
Main Authors: Sottero, Barbara, Gamba, Paola, Longhi, Monica, Robbesyn, Fanny, Abuja, Peter M., Schaur, Rudolf J., Poli, Giuseppe, Leonarduzzi, Gabriella
Format: Article
Language:English
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Summary:Abstract Within the broad variety of compounds generated via oxidative reactions in low density lipoproteins (LDL) and subsequently found in the atherosclerotic plaque, are aldehydes still esterified to the parent lipid and termed core‐aldehydes. The most represented cholesterol core‐aldehyde in LDL is 9‐oxononanoyl cholesterol (9‐ONC), an oxidation product of cholesteryl linoleate. Here we report that 9‐ONC, at concentration actually detectable in biological material, significantly up‐regulates the expression and the synthesis of the pro‐fibrogenic cytokine transforming growth factor β1 (TGFβ1) by cultured macrophages. As previously demonstrated for other lipid oxidation products present in LDL, namely a biologically representative mixture of oxysterols and the unesterified aldehyde 4‐hydroxynonenal, these effects on TGFβ1 by 9‐ONC further points to LDL lipid oxidation as a powerful source of pro‐fibrogenic stimuli.
ISSN:0951-6433
1872-8081
DOI:10.1002/biof.5520240125