Affiliations: Department of Clinical and Biological Sciences,
University of Torino, S. Luigi Hospital, Orbassano, Torino, Italy | Institute of Molecular Biology, Biochemistry and
Microbiology, University of Graz, Graz, Austria
Note: [] Address for correspondence: Gabriella Leonarduzzi, Department of
Clinical and Biological Sciences of the University of Torino, S. Luigi
Hospital, Regione Gonzole 10, 10043 Orbassano, Torino, Italy. Tel.: +39 011
6705434; Fax: +39 011 6705424; E-mail: gabriella.leonarduzzi@unito.it
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.
